Sulfonamide compounds and uses thereof

ABSTRACT

In accordance with the present invention, there is provided a novel class of sulfonamide compounds. Compounds of the invention contain a core sulfonamide group. Variable moieties connected to the sulfur atom and nitrogen atom of the sulfonamide group include substituted or unsubstituted hydrocarbyl moieties, substituted or unsubstituted heterocycle moieties, polycyclic moieties, halogen, alkoxy, ether, ester, amide, sulfonyl, sulfonamidyl, sulfide, carbamate, and the like. Invention compounds are capable of a wide variety of uses. For example sulfonamide compounds can act to modulate production of amyloid β protein and are useful in the prevention or treatment of a variety of diseases. Pharmaceutical compositions containing invention compounds are also provided. Such compositions have wide utility for the prevention or treatment of a variety of diseases.

This application is a 371 of PCT/US00//04560 filed in English on 22 Feb.2000 which claims the benefit of provisional application, 60,121,906,60,122,746, 60,122,748 filed Feb. 26, 1999, and 60/130,994, 60/130,995,both filed Apr. 23, 1999.

FIELD OF INVENTION

The present invention relates to novel compounds which contain asulfonamide moiety, and pharmaceutical compositions containing inventioncompounds. In addition, the present invention relates to therapeuticmethods for the treatment and prevention of various disease conditions,especially Alzheimer's disease and other diseases relating to thedeposition of amyloid.

BACKGROUND OF THE INVENTION

Alzheimer's disease (AD) is a progressive, neurodegenerative diseasecharacterized by memory loss, language deterioration, impairedvisuospatial skills, poor judgment, and indifferent attitude. It is themost common form of dementia, affecting nearly 50% of the elderlypopulation over 85 years of age. There is currently no effectivetreatment to prevent the disease.

One of the major histopathological hallmarks of Alzheimer's disease issenile plaques which are found only in the brain, and especially inregions associated with memory, reasoning and cognition. The majorconstituent of senile plaques is amyloid β protein, an insoluble 40-42amino acid polypeptide. Amyloid β protein is normally found in theplasma and cerebrospinal fluid of healthy individuals although itsfunction is unknown. In the disease state increased production and/orreduced removal of amyloid β protein results in increases in proteinlevels in plasma and cerebrospinal fluid and accumulation of the proteinin the brain.

Amyloid β protein is derived from amyloid precursor protein (APP) byproteolytic cleavage. Processing of APP to amyloid β protein and otherAPP cleavage fragments is governed by a group of enzymes termedsecretases. One type of secretase, γ-secretase, is responsible for theprotein cleavage that gives rise to amyloid β protein. Although theexistence of a protein having the activity of γ-secretase has beensuggested, neither the gene encoding the protein, nor the protein itselfhas been completely isolated and characterized.

Thus, there is a continuing need in the art for compounds that canspecifically inhibit proteolytic cleavage of APP, thereby inhibitingamyloid β protein production. The present invention meets this andrelated needs by providing a family of novel compounds and relatedmethods of use.

BRIEF DESCRIPTION OF THE INVENTION

In accordance with the present invention, we have discovered a class ofsulfonamide compounds that inhibit amyloid β protein production.Compounds of the invention contain a core sulfonamide group. Variablemoieties are connected to the sulfur atom and nitrogen atom of thesulfonamide group and include substituted or unsubstituted hydrocarbylmoieties, substituted or unsubstituted heterocyclic moieties, polycyclicmoieties, halogen, alkoxy, ether, ester, amide, sulfonyl, sulfonamidyl,sulfide, and carbamate.

Invention compounds are capable of a wide variety of uses. For example,invention sulfonamide compounds can act to modulate amyloid β proteinand are useful in the prevention and/or treatment of a variety ofdiseases. Without wishing to be bound by any theory, invention compoundsare believed to act by blocking the proteolytic processing pathways thatresult in the formation of amyloid β proteins. Invention compounds arebelieved to act by inhibiting proteolytic cleavage of amyloid precursorprotein (APP), the large precursor protein from which amyloid β proteinis derived. Therapeutic indications for compounds with this inhibitoryactivity include disorders of the central nervous system in whichamyloid β protein accumulates in the cerebral extracellular perivascularspace, such as Alzheimer's disease. Pharmaceutical compositionscontaining invention compounds also have wide utility.

DETAILED DESCRIPTION OF THE INVENTION

In accordance with the present invention, there are provided compoundshaving the structure:

-   -   and pharmaceutically acceptable salts thereof, wherein:    -   D is hydrogen, substituted or unsubstituted hydrocarbyl,        substituted or unsubstituted heterocycle optionally having one        or more double bonds, halogen, alkoxyl, ester, amide, or        -   D and G, taken together, form a substituted or unsubstituted            cyclic moiety; and        -   E, is hydrogen, substituted or unsubstituted hydrocarbyl,            substituted or unsubstituted heterocycle optionally having            one or more double bonds, alkoxyl, amide, sulfonyl,            sulfonamidyl, sulfide or alkoxyl; or        -   E and J, taken together, form a substituted or unsubstituted            cyclic moiety; and    -   G, when not part of a cyclic moiety including D, is substituted        or unsubstituted hydrocarbyl, substituted or unsubstituted        heterocycle optionally having one or more double bonds, amine,        amide, ester, ether or carbamate; and    -   J, when not part of a cyclic moiety including E, is substituted        or unsubstituted hydrocarbyl, heterocycle optionally having one        or more double bonds.

As employed herein, “hydrocarbyl” refers to straight chain, branchedchain and cyclic (ie., ring-containing) monovalent and bivalent radicalsderived from saturated or unsaturated moieties containing only carbonand hydrogen atoms. Straight and branched chain radicals have in therange of about 1 up to 12 carbon atoms and cyclic hydrocarbyl radicalshave in the range of about 3 up to about 20 carbon atoms. The term“substituted hydrocarbyl” refers to hydrocarbyl moieties further bearingsubstituents as set forth below.

Exemplary straight or branched chain hydrocarbyl moieties include alkylmoieties, alkenyl moieties, polyalkenyl (e.g., dialkenyl moieties, andtrialkenyl moieties), alkynyl moieties, alkadiynal moieties, alkatriynalmoieties, alkenyne moieties, alkadienyne moieties, alkenediyne moieties,and the like.

Exemplary cyclic hydrocarbyl moieties include cycloalkyl moieties,cycloalkenyl moieties, cycloalkadienyl moieties, cycloalkatrienylmoieties, cycloalkynyl moieties, cycloalkadiynyl moieties, aromaticmoieties, spiro hydrocarbon moieties wherein two rings are joined by asingle atom which is the only common member of the two rings (e.g.,spiro[3.4]octanyl, and the like), bicyclic hydrocarbon moieties whereintwo rings are joined and have at least two atoms in common (e.g.,bicyclo [3.2.1]octane, bicyclo [2.2.1]hept-2-ene, and the like), ringassemblies wherein two or more cyclic systems (i.e., single rings orfused systems) are directly joined to each other by single or doublebonds, and the number of such ring junctions is one less than the numberof cyclic systems involved (e.g., biphenylyl, biphenylylene, radicals ofp-terphenyl, cyclohexylbenzyl, and the like), polycyclic moieties, andthe like;

“alkyl” refers to straight or branched chain alkyl radicals having inthe range of about 1 up to 12 carbon atoms; “substituted alkyl” refersto alkyl radicals further bearing one or more substituents such ascycloalkyl, cycloalkenyl, aryl, heterocycle optionally having one ormore double bonds, halogen, alkoxy, cyano, cyanomethyl, nitro, amino,amide, amidine, hydroxy, carboxyl, carbamate, ether, ester, sulfonyl,sulfonamide, mercapto, and the like; “lower alkyl” refers to alkylradicals having in the range of about 1 up to 6 carbon atoms;“substituted lower alkyl” refers to lower alkyl radicals further bearingone or more substituents as set forth above;

“alkenyl” refers to straight or branched chain hydrocarbyl radicalshaving at least one carbon—carbon double bond, and having in the rangeof about 2 up to 12 carbon atoms, and “substituted alkenyl” refers toalkenyl radicals further bearing one or more substituents as set forthabove; “lower alkenyl” refers to alkenyl radicals having in the range ofabout 2 up to 6 carbon atoms; “substituted lower alkenyl” refers tolower alkenyl radicals further bearing one or more substituents as setforth above;

“alkynyl” refers to straight or branched chain hydrocarbyl radicalshaving at least one carbon—carbon triple bond, and having in the rangeof about 2 up to 12 carbon atoms, and “substituted alkynyl” refers toalkynyl radicals further bearing one or more substituents as set forthabove;

“cycloalkyl” refers to ring-containing radicals containing in the rangeof about 3 up to 20 carbon atoms, and “substituted cycloalkyl” refers tocycloalkyl radicals further bearing one or more substituents as setforth above;

“cycloalkenyl” refers to ring-containing radicals having at least onecarbon—carbon double bond in the ring, and having in the range of about3 up to 20 carbon atoms, and “substituted cycloalkenyl” refers to cyclicalkenyl radicals further bearing one or more substituents as set forthabove;

“cycloalkynyl” refers to ring-containing radicals having at least onecarbon—carbon triple bond in the ring, and having in the range of about7 up to 20 carbon atoms, and “substituted cycloalkynyl” refers to cyclicalkynyl radicals further bearing one or more substituents as set forthabove;

“aromatic” refers to hydrocarbyl radicals having one or morepolyunsaturated carbon rings having aromatic character, and having inthe range of about 6 up to about 14 carbon atoms, and “substitutedaromatic” refers to aromatic radicals further bearing one or moresubstituents as set forth above;

“aryl” refers to mononuclear aromatic radicals having 6 carbon atoms andfused ring aromatic radicals having up to about 14 carbon atoms, i.e.polynuclear aromatic radicals, and “substituted aryl” refers to arylradicals further bearing one or more substituents as set forth above;

“alkylene” refers to divalent alkyl moieties wherein said moiety servesto link two structures together; “substituted alkylene” refers toalkylene moieties further bearing one or more substituents as set forthabove;

“alkenylene”, refers to divalent alkenyl moieties wherein said moietyserves to link two structures together, “substituted alkenylene” refersto alkenylene moieties further bearing one or more substituents as setforth above;

“arylene” refers to divalent aryl moieties wherein said moiety serves tolink two structures together; “substituted arylene” refers to arylenemoieties further bearing one or more substituents as set forth above;

“heterocycle” refers to ring-containing monovalent and bivalent radicalshaving one or more heteroatoms (e.g., N, O, S) as part of the ringstructure, and having in the range of 3 up to 20 atoms in the rings.Heterocyclic moieties may be saturated or unsaturated containing one ormore double bonds, and may contain more than one ring. Heterocyclicmoieties include, for example, monocyclic moieties such as piperazinyl,morpholinyl, thiomorpholinyl, imidazolyl, pyrimidinyl, isothiazolyl,isoxazolyl, pyrazinyl, pyrimidinyl, pyrazolyl, pyrrolyl, furanyl,pyranyl, thienyl, isoimidazolyl, triazolyl, dithiolyl, oxadithiolyl,isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, pyronyl, dioxinyl,pyridinyl, pyridazinyl, triazinyl, oxazinyl, isoxazinyl, and the like,bicyclic heterocyclic moieties such as azabicycloalkanyl moieties,oxabicycloalkyl moieties, and the like, spiro compounds containingheteroatoms, and ring assemblies containing heteroatoms. The term“substituted heterocycle” refers to heterocycles further bearing one ormore substituents as set forth above. Exemplary radicals includeradicals of polycyclic, bicyclic and spiro heterocycles such as

“halogen” refers to fluoride, chloride, bromide or iodide radicals;

“cyclic moiety” refers to substituted and unsubstituted cyclichydrocarbyl moieties, as described above, and substituted andunsubstituted heterocycles, as described above;

“alkoxy” refers to radicals of the general formula —O—R, where R issubstituted or unsubstituted hydrocarbyl; exemplary alkoxy radicalsinclude methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy,t-butoxy, and the like;

“ether” refers to radicals of the general formula —R′—O—R″, where R′ andR″ are independently substituted or unsubstituted hydrocarbyl, orsubstituted or unsubstituted heterocycle optionally having one or moredouble bonds;

“ester” refers to radicals of the general formulae —C(O)O—R and—O—C(O)R, where R is substituted or unsubstituted hydrocarbyl,substituted or unsubstituted heterocycle optionally having one or moredouble bonds; it is understood that the carbon atom of the ester groupmay be linked directly to the moiety of which ester is a substituent, ormay be linked via a linker, such as substituted or unsubstitutedalkylene, alkenylene, arylene, and the like;

“amine” refers to radicals of the general formula —NRR′, R and R′ areindependently hydrogen, substituted or unsubstituted hydrocarbyl,substituted or unsubstituted heterocycle optionally having one or moredouble bonds, alkoxy, ether, ester, amide. Thus, the radical may be aprimary amine of the general formula, —NH₂, a secondary amine of thegeneral formula —NHR, or a tertiary amine of the general formula —NRR′.It is understood that R and R′ may cooperate to form a cyclic moietyhaving a nitrogen atom as a member of a ring, and that the nitrogen atomof the amine group may be linked directly to the moiety of which amineis a substituent, or may be linked via a linker, such as substituted orunsubstituted alkylene, alkenylene, arylene, and the like;

“amide” refers to radicals of the general formula —C(O)NRR′, wherein Rand R′ are independently hydrogen, substituted or unsubstitutedhydrocarbyl, substituted or unsubstituted heterocycle optionally havingone or more double bonds; it is understood that R and R′ may cooperateto form a cyclic moiety having a nitrogen atom as a member of a ring;and that the carbon atom of the amide group may be linked directly tothe moiety of which amide is a substituent, or may be linked via alinker, such as substituted or unsubstituted alkylene, alkenylene,arylene, and the like;

“sulfide” refers to radicals of the general formula —SR, wherein R issubstituted or unsubstituted hydrocarbyl, substituted or unsubstitutedheterocycle optionally having one or more double bonds, ester, amine,amide, and the like;

“sulfonyl” refers to moieties containing a sulfonyl radical (—SO₂—);

“sulfonamidyl” refers to moieties containing a sulfonamide radical(—SO₂.NRR′), wherein R and R′ are independently substituted orunsubstituted hydrocarbyl, substituted or unsubstituted heterocycleoptionally having one or more double bonds; it is understood that R andR′ may cooperate to form a cyclic moiety having a nitrogen atom as amember of a ring; and that the sulfur atom of the sulfonamide radicalmay be linked directly to the moiety of which amide is a substituent, ormay be linked via a linker, such as substituted or unsubstitutedalkylene, alkenylene, arylene, ether, ester, and the like;

“carbamate” refers to moieties containing a radical having the generalformula —O—C(O)—NRR′ wherein R and R′ are independently substituted orunsubstituted hydrocarbyl, substituted or unsubstituted heterocycleoptionally having one or more double bonds; it is understood that R andR′ may cooperate to form a cyclic moiety having a nitrogen atom as amember of a ring; and that the oxygen atom of the carbamate group may belinked directly to the moiety of which carbamate is a substituent, ormay be linked via a linker, such as substituted or unsubstitutedalkylene, substituted or unsubstituted alkenylene, ether, ester, and thelike;

In accordance with the present invention, D is hydrogen, substituted orunsubstituted hydrocarbyl, substituted or unsubstituted heterocycleoptionally having one or more double bonds, halogen, alkoxyl, ester oramide, or D and E, taken together, form a substituted or unsubstitutedcyclic moiety. In accordance with one embodiment of the invention, D issubstituted or unsubstituted hydrocarbyl. Moieties contemplated for usein this embodiment of the invention include those wherein D is hydrogenor substituted or unsubstituted lower alkyl, with hydrogen andunsubstituted lower alkyl preferred, and hydrogen and unsubstitutedmethyl especially preferred.

Further in accordance with the present invention, E is selected fromsubstituted or unsubstituted hydrocarbyl, heterocycle optionally havingone or more double bonds, alkoxyl, amide, sulfonyl, sulfonamidyl orsulfide. Presently preferred compounds of the invention are thosewherein E is substituted or unsubstituted alky, substituted orunsubstituted alkenyl, substituted or unsubstituted alkynyl, substitutedor unsubstituted cycloalkyl, substituted or unsubstituted heterocycleoptionally having one or more double bonds, substituted or unsubstitutedpolycyclic moiety, substituted or unsubstituted aryl, and the like.Especially preferred moieties include substituted or unsubstituted aryl;when E is substituted aryl, a mono substituted or di-substituted aryl ispreferred, and preferred substituents are halogen, ester, alkyl,sulfur-linked alkyl, NO₂, SO₂, and the like, with halogen especiallypreferred.

In accordance with the present invention, G is substituted orunsubstituted hydrocarbyl, substituted or unsubstituted heterocycleoptionally having one or more double bonds, amine, amide, ester, etheror carbamate. Thus, G can be substituted or unsubstituted alkyl,substituted or unsubstituted alkenyl, substituted or unsubstitutedalkynyl, substituted or substituted cycloalkyl, substituted orunsubstituted aryl, substituted or unsubstituted cyclic moiety, ester,amide, carboxylate, and the like.

In one embodiment of the invention, G is substituted or unsubstitutedalkyl, with substituted lower alkyl presently preferred. Presentlypreferred substituents are halogen and heterocycle optionally containingone or more double bonds such as imidazolyl, morpholinyl, pyrazolyl,pyrrolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, and5-methyltetrazolyl, and the like. In another embodiment of theinvention, G is substituted or unsubstituted alkenyl, with substitutedlower alkenyl preferred. A presently preferred substituent of loweralkenyl is halogen. In yet another embodiment of the invention, G isunsubstituted alkynyl, with lower unsubstituted alkynyl presentlypreferred. In still another embodiment of the invention, G isunsubstituted cycloalkyl.

In accordance with another embodiment of the invention, G is asubstituted or unsubstituted cyclic moiety. Presently preferred cyclicmoieties include substituted or unsubstituted naphthalenyl; whensubstituted, preferred substituents are ether moieties, especially1-piperidinyl propoxyl.

In accordance with still another embodiment of the invention, G is anester, represented by the formula —C(O)—OR. In presently preferredembodiments of the invention, R is substituted or unsubstituted loweralkyl or substituted aryl.

In accordance with another embodiment of the invention, G iscarboxylate.

In accordance with a further embodiment of the invention, G issubstituted or unsubstituted aryl. When G is substituted aryl, presentlypreferred substituents are substituted or unsubstituted alkyl,substituted or unsubstituted alkenyl, substituted or unsubstitutedalkynyl, halogen, amide, ester, hydroxy, sulfonamide, sulfonyl, ether,and radicals of the general formula —O—(CH₂)_(n)—S-aryl, wherein n is 1to 6.

In accordance with the present invention, J is a moiety attached to thesulfur atom of a sulfonamide group. J is substituted or unsubstitutedhydrocarbyl, heterocycle optionally having one or more double bonds, orJ and E, taken together, form a substituted or unsubstituted cyclicmoiety. Thus J can be substituted or unsubstituted alkyl, substituted orunsubstituted alkenyl, substituted or unsubstituted aryl, substituted orunsubstituted heterocycle optionally having one or more double bonds, orJ and E, taken together can form a substituted or unsubstitutedpolycyclic moiety or substituted or unsubstituted ring assembly.

In accordance with a particular embodiment of the invention, J issubstituted or unsubstituted alkyl, with substituted or unsubstitutedlower alkyl presently preferred. Substituents of alkyl presentlypreferred in this embodiment are substituted and unsubstituted aryl. Inaccordance with another embodiment of invention, J is substituted orunsubstituted alkenyl with substituted lower alkenyl preferred, and aryla preferred substituent.

In accordance with still another embodiment of the invention, J is asubstituted or unsubstituted polycyclic moiety. Thus J can be pentalene,indene, naphthalene, azulene, and the like. Moieties contemplated foruse in this embodiment of the present invention include substituted orunsubstituted naphthalene; preferred substituents are secondary andtertiary amines.

In accordance with yet another embodiment of the invention, J issubstituted or unsubstituted heterocycle optionally containing one ormore double bonds. Moieties contemplated for use in this embodiment ofthe invention include those where J is isothiazolyl, thiazolyl,thiazinyl, thiazepinyl, and the like, with substituted thiazolylpreferred.

In still another embodiment of the invention, J is substituted orunsubstituted aryl. When J is substituted, preferred substituentmoieties include alkyl, O-alkyl, —S-alkyl, —S-aryl, halogen, nitro andtrifluoromethyl.

In yet another embodiment of the invention, J cooperates with E to forma substituted or unsubstituted polycyclic moiety. Thus, J can be a fusedmoiety such as substituted or unsubstituted bicyclic, or a substitutedor unsubstituted ring assembly. Moieties contemplated for use in thisembodiment include substituted and unsubstituted naphthalenyl andsubstituted and unsubstituted biphenylyl.

Those of skill in the art will recognize that multiple isomers exist fora single chemical formula; each of the possible isomeric forms of thevarious empirical formulae set forth herein are contemplated by theinvention.

Those of skill in the art recognize that invention compounds may containone or more chiral centers, and thus can exist as racemic mixtures aswell as in individual enantiomeric forms. For many applications, it ispreferred to carry out stereoselective syntheses and/or to subject thereaction product to appropriate purification steps so as to producesubstantially optically pure materials. Suitable stereoselectivesynthetic procedures for producing optically pure materials are wellknown in the art, as are procedures for purifying racemic mixtures intooptically pure fractions. Those of skill in the art will furtherrecognize that invention compounds may exist in polymorphic formswherein a compound is capable of crystallizing in different forms.Suitable methods for identifying and separating polymorphisms are knownin the art.

In accordance with another embodiment of the present invention, thereare provided pharmaceutical compositions comprising sulfonamidecompounds as described above, in combination with pharmaceuticallyacceptable carriers. Optionally, invention compounds can be convertedinto non-toxic acid addition salts, depending on the substituentsthereon. Thus, the above-described compounds (optionally in combinationwith pharmaceutically acceptable carriers) can be used in themanufacture of medicaments useful for the treatment of a variety ofindications.

“Pharmaceutically acceptable salt” refers to a salt of the compound usedfor treatment which possesses the desired pharmacological activity andwhich is physiologically suitable. The salt can be formed with organicacids such as acetate, adipate, alginate, aspartate, benzoate,benzenesulfonate, butyrate, citrate, camphorate, camphorsulfonate,cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate,fumarate, glucoheptanoate, glycerophosphate, heptanoate, hexanoate,2-hydroxyethanesulfonate, lactate, malate, maleate, methanesulfonate,2-naphthalenesulfonate, nicotinate, oxalate, tartrate, toluenesulfonate,undecanoate, and the like. The salt can also be formed with inorganicacids such as sulfate, bisulfate, chlorate, perchlorate, hemisulfate,hydrochloride, hydrobromide, hydroiodide, and the like. In addition, thesalt can be formed with a base salt, including ammonium salts, alkalimetal salts such as sodium salts, potassium salts, and the like;alkaline earth metal salts such as calcium salts, magnesium salts, andthe like; salts with organic bases such as dicyclohexylamine salts,N-methyl-D-glucamine, phenylethylamine, and the like; and salts withamino acids such as arginine, lysine, and the like.

Sulfonamide compounds as described above can be readily prepared usingsynthetic chemistry techniques known to those of skill in the art. Seethe Examples section herein for detailed description of numerousexemplary synthetic protocols.

In accordance with the present invention, a method of modulating thelevel of Amyloid Precursor Protein (APP) is provided. The methodincludes contacting APP with at least one sulfonamide compound accordingto the invention. As employed herein, the phrase “modulating the levelof refers to altered levels of protein so that the level is different asa result of employing the invention method when compared to the levelwithout employing the invention method. Modulating the level of APPincludes the suppression or augmentation of the level of any one of anumber of APP proteins such as a full-length APP, APP proteins havingdeletions, additions or substitutions of amino acids, APP proteins thatare fragments of full-length APP protein, soluble APP (s-APP), insolubleAPP, and the like. Exemplary APP proteins include APP₇₇₀, APP₇₅₁,APP_(695wt), APP_(670/671), APP_(670/671/717), sAPP, α-sAPP, β-sAPP, andthe like.

A variety of APP proteins are found in neural and non-neural tissues.APP₇₇₀ and APP₇₅₁ are wild-type APPs of 770 and 751 amino acid residues,respectively, that are found in non-neural tissues. APP_(695wt) is anAPP of 695 residues that is expressed in neurons. APP_(670/671), ishuman APP, 695 residues in length, that has mutations at codons 670 and671 (Swedish double mutation). APP_(670/671/717) is a similar toAPP_(670/671) with an additional mutation at codon 717 (Phe for Val).sAPP is soluble APP, α-sAPP is α-secretase-cleaved soluable APP andβ-sAPP is β-secretase-cleaved APP.

In accordance with another embodiment of the invention, there areprovided methods of treating a wide variety of disease conditions, saidmethod comprising administering to a patient in need thereof atherapeutically effective amount of at least one of the sulfonamidecompounds described above.

APP is believed to be involved in numerous disease states. Therefore,modulating the level of APP also provides a variety of therapeuticapplications, such as the treatment of amyloid angiopathy, cerebralamyloid angiopathy, systemic amyloidosis, Alzheimer's disease,hereditary cerebral hemorrhage with amyloidosis of the Dutch type,inclusion body myositis, Down's syndrome, and the like.

As used herein, “treating” refers to inhibiting or arresting thedevelopment of a disease, disorder or condition and/or causing thereduction, remission, or regression of the symptoms of a disease,disorder or condition. Those of skill in the art will understand thatvarious methodologies and assays may be used to assess the developmentof a disease, disorder or condition, and similarly, variousmethodologies and assays may be used to assess the reduction, remissionor regression of a disease, disorder or condition.

As used herein, “administering” refers to means for providingsulfonamide compounds and/or salts thereof, optionally employingpharmaceutically acceptable carriers, as described herein, to a patient,using any suitable method of delivery, e.g., oral, sublingualintravenous, subcutaneous, transcutaneous, intramuscular,intracutaneous, intrathecal, epidural, intraoccular, intracranial,inhalation, rectal, vaginal, and the like administration. Administrationin the form of creams, lotions, tablets, capsules, pellets, dispersiblepowders, granules, suppositories, syrups, elixirs, lozenges, injectablesolutions, sterile aqueous or non-aqueous solutions, suspensions oremulsions, patches, and the like, is also contemplated. The activeingredients may be compounded with non-toxic, pharmaceuticallyacceptable carriers including, glucose, lactose, gum acacia, gelatin,mannitol, starch paste, magnesium trisilicate, talc, corn starch,keratin, colloidal silica, potato starch, urea, dextrans, and the like.

“Contacting” as employed herein may include administering in solution orin solid phase.

For purposes of oral administration, tablets, capsules, troches, aqueousor oily suspensions, dispersible powders or granules, emulsions, hard orsoft capsules, or syrups, elixirs and lozenges containing variousexcipients such as calcium carbonate, lactose, calcium phosphate, sodiumphosphate, and the like may be employed along with various granulatingand disintegrating agents such as corn starch, potato starch, alginicacid, and the like, together with binding agents such as gum tragacanth,corn starch, gelatin, acacia, and the like. Lubricating agents such asmagnesium striethylaminerate, striethylamineric acid, talc, and the likemay also be added. Preparations intended for oral use may be preparedaccording to any methods known to the art for the manufacture ofpharmaceutical preparations and such preparations may contain one ormore agents selected from the group consisting of a sweetening agentsuch as sucrose, lactose, saccharin, and the like, flavoring agents suchas peppermint, oil of wintergreen, and the like, coloring agents andpreserving agents in order to provide pharmaceutically palatablepreparations. Preparations for oral use may also contain suitablecarriers include emulsions, solutions, suspensions, syrups, and thelike, optionally containing additives such as wetting agents,emulsifying and suspending agents, sweetening, flavoring and perfumingagents, and the like. Tablets may be uncoated or they may be coated byknown techniques to delay disintegration and absorption in thegastrointestinal tract and thereby provide a sustained action over alonger period of time.

For the preparation of oral liquids, suitable carriers includeemulsions, solutions, suspensions, syrups, and the like, optionallycontaining additives such as wetting agents, emulsifying and suspendingagents, sweetening, flavoring and perfuming agents, and the like.

For the preparation of fluids for parenteral administration, suitablecarriers include sterile aqueous or non-aqueous solutions, suspensions,or emulsions. For parenteral administration, solutions for the practiceof the invention may comprise sterile aqueous saline solutions, or thecorresponding water soluble pharmaceutically acceptable metal salts, aspreviously described. For parenteral administration, solutions of thecompounds used in the practice of the invention may also comprisenon-aqueous solutions, suspensions, emulsions, and the like. Examples ofnon-aqueous solvents or vehicles are propylene glycol, polyethyleneglycol, vegetable oils, such as olive oil and corn oil, gelatin, andinjectable organic esters such as ethyl oleate, and the like. Suchdosage forms may also contain adjuvants such as preserving, wetting,emulsifying, and dispersing agents. They may be sterilized, for example,by filtration through a bacteria-retaining filter, by incorporatingsterilizing agents into the compositions, by irradiating thecompositions, or by heating the compositions. They can also bemanufactured in the form of sterile water, or some other sterileinjectable medium immediately before use.

Aqueous solutions may also be suitable for intravenous, intramuscular,intrathecal, subcutaneous, and intraperitoneal injection. The sterileaqueous media employed are all readily obtainable by standard techniqueswell known to those skilled in the art. They may be sterilized, forexample, by filtration through a bacteria-retaining filter, byincorporating sterilizing agents into the compositions, by irradiatingthe compositions, by heating the compositions, and the like. They canalso be manufactured in the form of sterile water, or some other sterilemedium capable of injection immediately before use.

Compounds contemplated for use in the practice of the present inventionmay also be administered in the form of suppositories for rectal orvaginal administration. These compositions may be prepared by mixing thedrug with a suitable non-irritating excipient, such as cocoa butter,synthetic glyceride esters of polyethylene glycols, and the like, suchmaterials being solid at ambient temperatures but liquify and/ordissolve in internal cavities to release the drug.

The preferred therapeutic compositions for inocula and dosage will varywith the clinical indication. Some variation in dosage will necessarilyoccur depending upon the condition of the patient being treated, and thephysician will, in any event, determine the appropriate dose for theindividual patient. The effective amount of compound per unit dosedepends, among other things, on the body weight, physiology, and choseninoculation regimen. A unit dose of compound refers to the weight ofcompound without the weight of carrier (when carrier is used).

The route of delivery compounds and compositions used for the practiceof the invention is determined by the disease and the site wheretreatment is required. Since the pharmacokinetics and pharmacodynamicsof the compounds and compositions described herein will vary somewhat,the most preferred method for achieving a therapeutic concentration in atissue is to gradually escalate the dosage and monitor the clinicaleffects. The initial dose, for such an escalating dosage regimen oftherapy, will depend upon the route of administration.

In accordance with invention methods, the medicinal preparation can beintroduced parenterally, by dermal application, and the like, in anymedicinal form or composition. It is used as a solitary agent ofmedication or in combination with other medicinal preparations. Singleand multiple therapeutic dosage regimens may prove useful in therapeuticprotocols.

As employed herein, the phrase “a therapeutically effective amount”,when used in reference to invention methods employing sulfonamidecompounds and pharmaceutically acceptable salts thereof, refers to adose of compound sufficient to provide circulating concentrations highenough to impart a beneficial effect on the recipient thereof. Thespecific therapeutically effective dose level for any particular patientwill depend upon a variety of factors including the disorder beingtreated, the severity of the disorder, the activity of the specificcompound used, the route of administration, the rate of clearance of thespecific compound, the duration of treatment, the drugs used incombination or coincident with the specific compound, the age, bodyweight, sex, diet and general health of the patient, and like factorswell known in the medical arts and sciences. Dosage levels typicallyfall in the range of about 0.001 up to 100 ing/kg/day; with levels inthe range of about 0.05 up to 10 mg/kg/day being preferred.

In still another embodiment of the invention, there are provided methodsfor preventing disease conditions in a subject at risk thereof, saidmethod comprising administering to said subject a therapeuticallyeffective amount of at least one of the sulfonamide compounds describedabove.

As used herein, the phrase “preventing disease conditions” refers topreventing a disease, disorder or condition from occurring in a subjectwho may be at risk for the disease, but has not yet presented anysymptoms thereof. Those of skill in the art will understand that avariety of methods may be used to determine a subject at risk for adisease, and that whether a subject is at risk for a disease will dependon a variety of factors known to those of skill in the art, includinggenetic make-up of the subject, age, body weight, sex, diet, generalphysical and mental health, occupation, exposure to environmentalconditions, marital status, and the like, of the subject.

“Subject in need thereof” is intended to mean a mammal, e.g., humans,domestic animals and livestock, having or at risk of having one or morediseases associated with a modified level of APP.

Those of skill in the art can readily identify a variety of assays thatcan be used to assess the activity of sulfonamide compounds of theinvention. For example, one can use in vitro cell-based assays to assessamyloid β protein production in cells that are exposed to inventioncompounds compared to cells exposed to control conditions. For suchassays, transfected cells that stably express various forms of APP andfrom which amyloid β protein is secreted are used. Methods to measureamyloid β protein, such as immunoprecipitation, enzyme-linkedimmunosorbant assay (ELISA) and radioimmunoassay, and the like are knownin the art. Immunoprecipitation methodology can be used to detectradiolabeled amyloid β protein derived from transfected cells having³⁵S-methionine-labeled APP (Haass et al., (1992) Nature, 32:322-325 andShoji et al. (1992) Science, 258:126-129). ELISA can be used to detectunlabeled amyloid β protein (Seubert et al. (1992) Nature, 359:325-327).

The invention will now be described in greater detail by reference tothe following non-limiting examples.

EXAMPLE 1 (S)-5-[[dimethyl(1,1-dimethylethyl)silyl]oxy]-1-pentanol

To a stirred solution of (4S)-pentane-1,4-diol [CAS 24347-57-7] (21.0 g,0.202 mol) and t-butyldimethylsilyl chloride (30.5 g, 0.202 mol) inCH₂Cl₂ (400 mL) was added triethylamine (43.0 mL, 0.305 mol) followed by4-(dimethylamino)pyridine (2.50 g, 20.2 mmol) at 0° C. The mixture wasstirred for 3 h at 0° C. and was diluted with diethyl ether (300 mL).The white precipitate was filtered and washed with diethyl ether. Thefiltrate was concentrated under reduced pressure. The pale yellow oilwas distilled (100° C.-103° C. at 0.7 mm) to afford the title compound(41 g, 92%) as a colorless oil.

¹H NMR (CDCl₃) δ 3.81 (m, 1H), 3.65 (m, 2H), 1.48-1.63 (m, 4H), 1.19 (d,3H), 0.91 (s, 9H), 0.07 (s, 6H).

EXAMPLE 24-Chloro-2-nitro-1-[[(tetrahydro-2H-pyran-2-yl)oxy]methyl]benzene

A magnetically stirred solution of 4-chloro-2-nitrobenzyl alcohol (25.0g, 133 mmol) and 3,4-dihydro-2H-pyran (118.2 mL, 16.8 g, 200 mol) inanhydrous dichloromethane (250 mL) was treated at 25° C. with pyridinium(toluenesulfonate (PPTS, 50 mg). The solution was stirred for 12 h,washed with 1 N NaOH (250 mL), brine (250 mL), dried (K₂CO₃), filtered,and concentrated in vacuo. Silica gel chromatography (4:1 hexane:ethylacetate) of the concentrate gave 22.5 g (62%) of the title compound asan oil.

EXAMPLE 3 5-Chloro-2-[[(tetrahydro-2H-pyran-2-yl)oxy]methyl]benzenamine

A Parr bottle containing4-chloro-2-nitro-1-[[(tetrahydro-2H-pyran-2-yl)oxy]methyl]benzene (22.6g, 82.8 mmol) and ethanol (150 mL) was treated with Raney nickel (50%slurry in water, 2.0 g), charged with hydrogen (60 psi) and rocked untilhydrogen uptake ceased (3 h). The resultant suspension was filteredthrough celite, and the celite cake thoroughly washed with fresh ethanol(5×150 mL). The combined organic extracts were concentrated in vacuo togive an orange oil that crystallized on standing. Recrystallization(ethyl acetate/hexane) gave the title compound as a white solid (19.64g, 98%). ¹H NMR (CDCl₃) δ7.00 (d, J=8 Hz, 1H), 6.65-6.60 (m, 2H), 4.72(A of ABq, J=12 Hz, 1H), 4.79-4.77 (m, 1H), 4.45 (B of ABq, J=12 Hz,1H), 4.27 (bs, 2H), 3.94-3.85 (m, 1H), 3.58-3.50 (m, I), 1.88-1.65 (m,2H), 1.58-1.46 (m, 4H).

EXAMPLE 4 4-Chloro-N-[5-chloro-2-hydroxymethyl)phenyl]benzenesulfonamide

To a magnetically stirred solution of5-chloro-2-[[(tetrahydro-2H-pyran-2-yl)oxy)methyl]benzenamine (4.38 g,18.1 Immunol) in anhydrous pyridine (100 mL) at 25° C. was added4-chlorobenzenesulfonyl chloride (3.82 g, 18.1 mmol). The solution wasstirred for 24 h and concentrated in vacuo. The residue was dissolved indichloromethane (150 mL), washed with brine (3×150 mL) and concentratedin vacuo. Silica gel chromatography (6:1 hexane:ethyl acetate) of theconcentrate afforded the title compound (5.27 g, 76%) as a crystallinesolid. ¹H NMR (CDCl₃) δ8.70 (bs, 1H), 7.71 (d, J=8.5 Hz, 2H), 7.58 (s,1H), 7.39 (d, J=8.5 Hz, 2H), 7.05-6.99 (m, 2H), 4.52-4.48 (m, 1H), 4.31(A of ABq, J=12 Hz, 1H), 4.24 (B of ABq, J=12 Hz, 1H), 4.13-4.05 (m,1H), 3.63-3.55 (m, 1H), 1.88-1.71 (m, 2H), 1.62-1.45 (m, 4H).

EXAMPLE 54-Chloro-N-[5-chloro-2-[[O-(2-tetrahydropyranyl)methyl]phenyl]]-N-[[4-[dimethyl(1,1-dimethylethyl)silyl]oxy]-1(R)-methylbutyl]benzenesulfonamide

To a solution of4-chloro-N-[5-chloro-2-[O-(2-tetrahydropyranyl)methyl]phenyl]benzenesulfonamide(2.70 g, 6.40 mmol), triphenylphosphine (3.40 g, 12.8 mmol) and(S)-5-[[dimethyl(1,1-dimethylethyl)silyl]oxy]-2-pentanol (2.40 g, 12.8mmol) in THF (25 mL) was added diisopropylazodicarboxylate (2.40 mL,12.8 mmol) dropwise at 0° C. under nitrogen atmosphere. The resultingmixture was allowed to warm to 22° C. with stirring. Stirring wascontinued for a period of 18 h and diethyl ether (100 mL) was added. Thewhite solid was filtered, washed with ether (50 mL), and the combinedether solution was concentrated under reduced pressure. Silica gelchromatography (3:17 ethyl acetate:hexanes) of the concentrate affordedthe tide compound (4.00 g, 100%) as a colorless oil. MS (ESI) m/e 615(M−H).

EXAMPLE 64-Chloro-N-[5-chloro-2-[[O-(2-tetrahydropyranyl)methyl]phenyl]]-N-(4-hydroxy-1-methylbutyl)benzenesulfonamide

To a solution of4-chloro-N-[5-chloro-2-[[O-(2-tetrahydropyranyl)methyl]phenyl]]-N-[[4-[dimethyl(1,1-dimethylethyl)silyl]oxy]-1-methylbutyl]benzenesulfonamide (3.80 g, 6.40 mmol) in THF (10 mL) was added 1Mtetrabutylammonium fluoride (10 mL, 10 mmol) at 0° C. The resultingsolution was allowed to stir at 0° C. for 2 h and concentrated underreduced pressure. Silica gel chromatography (1:1 ethyl acetate:hexane)of the concentrate afforded the title compound (3.20 g, 100%) as acolorless oil. MS (ESI) m/e 500 (M−H).

EXAMPLE 74-Chloro-N-[5-chloro-2-[[O-(2-tetrahydropyranyl)methyl]phenyl]]-N-(4-bromo-1-methylbutyl)benzenesulfonamide

To a solution of4-chloro-N-[5-chloro-2-[[O-(2-tetrahydropyranyl)methyl]phenyl]]-N-(4-hydroxy-1′-methylbutyl)benzenesulfonamide(3.20 g, 6.40 mmol) and triphenylphosphine (2.1 o g, 8.03 mmol) inmethylene chloride (30 mL) was added carbon tetrabromide (2.60 mL, 8.03mmol) dropwise at 0° C. The resulting solution was allowed to stir andwarm to 22° C. for 12 h. A saturated solution of ammonium chloride (25mL) was added. The reaction was extracted with methylene chloride (2×100mL). The organic phase was dried over Na₂SO₄, filtered, and concentratedunder reduced pressure. Silica gel chromatography (3:17 ethylacetate:hexanes) of the concentrate afforded the title compound (2.10 g,56%) as a colorless oil. MS (ESI) m/e 564 (M+H).

EXAMPLE 84-Chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[(R)-1-methyl-4-[(1,1-dimethylethyl)dimethylsilyl)oxy)butyl]benzenesulfonamide

To a solution of4-chloro-N-[5-chloro-2-(acetoxyoxymethyl)phenyl]benzenesulfonamide (13.7g, 36.6 mmol), triphenylphosphine (21.1 g, 80.6 mmol) and5S-[[(1,1-dimethylethyl)dimethylsilyl]oxy-2-pentanol (16.0 g, 73.3 mmol)in THF (130 mL) was added diisopropylazodicarboxylate (15.9 mL, 80.6mmol) dropwise at 0° C. under nitrogen. The resulting mixture wasallowed to warm to 22° C. with stirring. Stirring was continued for aperiod of 12 h followed by the addition of 150 ml of H₂O. The mixturewas extracted with ether (3×100 mL). The combined organic extracts werewashed with 1M NaHCO₃ and sat. brine. The organic phase was dried overNa₂SO₄, filtered, and concentrated under reduced pressure. Silica gelchromatography (1:5 ethyl acetate:hexanes) of the concentrate afforded16.6 g of4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[(R)-1-methyl-4-[(1,1-dimethylethyl)dimethylsilyl]oxy)butyl]benzenesulfonamideas a yellow oil in 79% yield.

EXAMPLE 94-Chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[(R)-1-methyl-4-hydroxybutyl]benzenesulfonamide

To a solution of 4chloro-N-[5-chloro-2-(acetoxymethyl)phenyl-N-[(R)-1-methyl-4-[(1,1-dimethylethyl)dimethylsilyl]oxy)butyl]benzenesulfonamide(15.9 g, 27.8 mmol) in acetonitrile (45 mL) was added 48% aqueous HF (16mL) dropwise at 0° C. The resulting solution was stirred for lb at 0° C.followed by addition of 50 mL of 1M NaHCO₃. The product was extractedwith ether (2×50 mL), dried over Na₂SO₄, filtered, and concentratedunder reduced pressure. Silica gel chromatography (ethyl acetate) of theconcentrate afforded 10.4 g of4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[(R)-1-methyl-4-hydroxybutyl]benzenesulfonamideas a colorless oil in 81% yield.

EXAMPLE 104-Chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamide

To a solution of4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[(R)-1-methyl-4-hydroxybutyl]benzenesulfonamide(500 mg, 1.09 mmol) in acetonitrile (2 mL) was added triphenylphosphine(571 mg, 2.18 mmol) and carbon tetrabromide (720 mg, 2.18 mmol) at 0° C.The resulting mixture was allowed to stir at 22° C. for 12 h followed bythe addition of 25 mL of sat. ammonium chloride. The product wasextracted with ether (2×25 mL), dried over Na₂SO₄, filtered, andconcentrated under reduced pressure. Silica gel chromatography (1:4ethyl acetate:hexanes) of the concentrate afforded 479 mg of4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamideas a colorless oil in 84% yield.

EXAMPLE 11(4R)-4-[5-chloro-2-(acetoxymethyl)phenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonicAcid

To a solution of4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[(R)-1-methyl-4-bromobutyl]benznesulfonamide(1.00 g, 1.91 mmol) in methanol/water (1:1, 4 mL) was added Na₂SO₃(0.723 g, 5.74 mmol). The mixture was heated to reflux for 12 hours andthen evaporated under reduced pressure. 2M HCl (25 mL) was added to theresulting oil. This mixture was extracted with CH₂Cl₂ (2×50 mL), driedover Na₂SO₄, and filtered. Solvent was concentrated under reducedpressure to afford(4R)-4-[5-chloro-2-(acetoxymethyl)phenyl][4-chlorophenyl)sulfonyl]-amine]pentylsulfonicacid (821 mg) as colorless oil in 88% yield. MS (ESI), 526 (M+1).

EXAMPLE 12(4R)-4-[5-chloro-2-(hydroxymethyl)phenyl](4-chlorophenyl)sulfonyl]-amino]pentylsulfonylChloride

To a solution of(4R)-4-[5-chloro-2-(acetoxymethyl)phenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonicacid (560 mg, 1.07 mmol) in benzene (5 mL) was added phosphoruspentachloride (445 mg, 2.14 mmol) at 22° C. The mixture was heated toreflux for 2 hours. This mixture was concentrated under reduced pressureand rediluted with CH₂Cl₂ (100 mL). This solution was washed with water(100 mL), dried over Na₂SO₄ and filtered. The organic solution wasconcentrated to afford 442 mg of(4R)-4-[5-chloro-2-(acetoxymethyl)phenyl](4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride as a pale yellow oil in 76% yield.

EXAMPLE 134-Chloro-N-[5-chloro-2-chlorophenyl]-N-[(R)-1-methyl-4-[(1,1-dimethylethyl)dimethylsilyl]oxy)butyl]benzenesulfonamide

To a solution of 4-chloro-N-[5-chloro-2-chlorophenyl]benzenesulfonamide(1.00 g, 2.97 mmol), triphenylphosphine (1.64 g, 6.24 mmol) and5S-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-2-pentanol (1.30 g, 5.94mmol) in THF (12 mL) was added diisopropylazodicarboxylate (1.23 mL,6.24 mol) dropwise at 0° C. under nitrogen. The resulting mixture wasallowed to warm to 22 DC with stirring. Stirring was continued for aperiod of 12 h followed by the addition of 25 mL of H₂O. The mixture wasextracted with ether (3×25 mL). The combined organic extracts werewashed with 1M NaHCO₃ and sat. brine. The organic phase was dried overNa₂SO₄, filtered, and concentrated under reduced pressure. Silica gelchromatography (1:5 ethyl acetate:hexanes) of the concentrate afforded830 mg of4-chloro-N-[5-chloro-2-chlorophenyl]-N-[(R)-1-methyl-4-[(1,1-dimethylethyl)-dimethylsilyl]oxy)butyl]benzenesulfonamideas a yellow oil in 52% yield.

EXAMPLE 144-Chloro-N-[5-chloro-2-chlorophenyl]-N-[(R)-1-methyl-4-hydroxybutyl]benzenesulfonamide

To a solution of4-chloro-N-[5-chloro-2-chlorophenyl]-N-[(R)-1-methyl-4-[(1,1-dimethylethyl)dimethylsilyl]oxy)butyl]benzenesulfonamide(650 mg, 1.21 mmol) in acetonitrile (4 mL) was added 48% aqueous HF (2mL) dropwise at 0° C. The resulting solution was stirred for 1 h at 0°C. followed by addition of 10 ml of 1M NaHCO₃. The product was extractedwith ether (2×25 mL), dried over Na₂SO₄, filtered, and concentratedunder reduced pressure. Silica gel chromatography (ethyl acetate) of theconcentrate afforded 430 mg of4-chloro-N-[5-chloro-2-chlorophenyl]-N-[(R)-1-methyl4-hydroxybutyl]benzenesulfonamide as a yellow oil in 84% yield.

EXAMPLE 154-Chloro-N-2,5-dichlorophenyl)-N-(3-(carboxy)-1(R)methylpropyl)benzenesulfonamide

4-chloro-N-[5-chloro-2-chlorophenyl]-N-[(R)₇-methyl-4-hydroxybutyl]benzenesulfonamide(1.57 g, 0.0037 moles) was dissolved in acetonitrile (25 mL) and water(2 mL). RuCl₃ (50 mg), and NaIO₄ (1.19 g, 0.0056 moles, 1.5 eq) wereadded and the mixture was stirred at room temperature for 18 hours. Themixture was filtered, concentrated, dissolved in CH₂Cl₂, washed with 1NHCl, dried over Na₂SO₄ and evaporated. Chromatography over silica gelusing 50-100% ethyl acetate/Hexane gave pure product (1.00 g, 62%) as abeige solid.

EXAMPLE 164-Chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamide

To a solution of4-chloro-N-[2,5-dichlorophenyl]-N-[R]-1-methyl-4-hydroxybutyl]benzene-sulfonamide(3.90 g, 9.20 mmol) in CH₂Cl₂ (20 mL) was added triphenylphosphine (4.87g, 18.4 mmol) and carbon tetrabromide (6.09 g, 18.4 mmol) at 0° C. Theresulting mixture was allowed to stir at 22° C. overnight. To thereaction was added sat. ammonium chloride (200 mL). The product wasextracted with CH₂Cl₂ (2×200 mL), dried over Na₂SO₄, filtered, andconcentrated under reduced pressure. Silica gel chromatography (1:4ethyl acetate:hexanes) of the concentrate afforded 3.13 g of4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamideas a colorless oil in 70% yield. MS (ESI) 486 (M+H).

EXAMPLE 17(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amine]pentylsulfonicAcid

To a solution of4-chloro-N-[5-chloro-2-chlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzne-sulfonamide(2.85 g, 5.88 mmol) in methanol/water (1:1, 12 mL) was added Na₂SO₃(7.40 g, 58.8 mmol). The mixture was heated to reflux for 12 hours andthen evaporated under reduced pressure. 2M HCl was added to theresulting oil. This mixture was extracted with CH₂Cl₂ (2×50 mL), driedover Na₂SO₄, and filtered. Solvent was concentrated under reducedpressure to afford (4R)-4-[2,5dichlorophenyl][4-chlorophenyl)sulfonyl]-amine]pentylsulfonic acid (2.34g) as colorless oil in 82% yield. MS (ESI) 486 (M+1).

EXAMPLE 18(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylChloride

To a solution of(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]amino]pentylsulfonicacid (2.34 g, 4.80 mmol) in benzene (10 mL) was added phosphoruspentachloride (1.48 g, 7.21 mmol) at 22° C. The mixture was heated toreflux for 2 hours. This mixture was concentrated under reduced pressureand rediluted with CH₂Cl₂ (120 mL). This solution was washed with water(100 mL), dried over Na₂SO₄ and filtered. The organic solution wasconcentrated to afford 2.21 g of (4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonyl chlorideas pale yellow oil in 91% yield. LC/MS 504.

EXAMPLE 194-Chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-azidobutyl]benzenesulfonamide

To a solution of4-chloro-N-[2,5-dichlorophenyl]-N-[R]-1-methyl-4-bromobutyl]benzene-sulfonamide(1.06 g, 2.50 mmol) in DMF (2.5 mL) was added diphenylphosphoryl azide(1.08 mL, 5.00 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.935 mL,6.25 mmol) at 0° C. The resulting mixture was allowed to stir at 100° C.overnight. To the reaction was added sat. ammonium chloride (200 mL).The product was extracted with CH₂Cl₂ (2×100 mL), dried over Na₂SO₄,filtered, and concentrated under reduced pressure. Silica gelchromatography (1:4 ethyl acetate:hexanes) of the concentrate afforded977 mg of4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-azidobutyl]-benzenesulfonamideas a colorless oil in 87% yield. MS (ESI) 447 (M+H).

EXAMPLE 204-Chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-aminobutyl]benzenesulfonamide

To a solution of4-chloro-N-[2,5-dichlorophenyl]-N-[R]-1-methyl-4-azidobutyl]benzene-sulfonamide(1.20 g, 2.68 mmol) in THF (5 mL) was added a THF solution of lithiumaluminum hydride (1.0 M, 2.68 mL) at −20° C. The resulting mixture wasallowed to stir at −20° C. overnight. To the reaction was added 0.5MNaOH (6 mL). This mixture was filtered through celite, dried overNa₂SO₄, filtered, and concentrated under reduced pressure. Silica gelchromatography (1:9 methanol/CHCl₃) of the concentrate afforded 972 mgof4-chloro-N-[2,5-dichlorophenyl)-N-[(R)-1-methyl-4-aminobutyl]benzenesulfonamideas a colorless oil in 86% yield. MS (ESI) 421 (M+H).

EXAMPLE 21 (S-[3-[(1,1-dimethylethyl)dimethylsilyl]oxy]-2-propanol

To a solution of (S)-1,2-propanediol (20.0 g, 0.263 mol), triethylamine(31.9 g, 0.315 mol), 4-dimethylaminopyridine (1.28 g, 10.5 mmol) inCH₂Cl₂ (200 mL) was added tert-butyldimethylsiloxy chloride (47.3 g,0.315 mol) at 22° C. The mixture was allowed to stir for 18 h. Themixture was diluted with CH₂Cl₂, washed with water and sat. aqueousNH₄Cl. The organic solution was dried over Na₂SO₄, filtered andconcentrated under reduced pressure. Silica gel chromatography (5% ethylacetate/hexanes) of the concentrate gave 45.0 g of the title compound asa clear oil in 90% yield.

EXAMPLE 224-Chloro-N-(2,5-dichlorophenyl)-N-[(R)-1-methyl-4-[(1,1-dimethylethyl)dimethylsilyl]ethyl]benezenesulfonamide

To a solution of 4-chloro-N-[2,5-dichlorophenyl]benzenesulfonamide (5.74g, 17.1 mmol), triphenylphosphine (6.70 g, 25.7 mmol),(S)-[3-[(1,1-dimethylethyl)dimethylsilyl]oxy]-2-propanol (4.90 g, 25.7mmol) in THF (50 mL) was added diisopropylazodicarboxylate (5.19 g, 25.7mmol) dropwise at 0° C. under nitrogen atmosphere. The resulting mixturewas allowed to warm to 22° C. Stirring was continued for a period of 18h followed by the addition of water. The mixture was extracted withdiethyl ether. The combined organic extracts were washed with NaHCO₃,sat. brine and dried over Na₂SO₄. Silica gel chromatography (1:10 ethylacetate:hexanes) of the concentrate produced the title compound in 90%yield.

EXAMPLE 234-Chloro-N-(2,5-dichlorophenyl)-N-[(R)-1-methyl-(2-hydroxyethyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-dichlorophenyl)-N—(R)-1-methyl-[[4-(1,1-dimethylethyl)dimethylsilyl]oxy]ethyl]benzenesulfonamide (07.80 g, 15.3 mmol) in CH₃CNwas added HF (5.5 mL) at 0° C. The resulting mixture was allowed to stirat 0° C. for 2 h and concentrated under reduced pressure. Silica gelchromatography (1:1 ethyl acetate:hexanes) of the concentrate affordedthe title compound (5.70 g, 95%/o) as a colorless oil.

EXAMPLE 244-Chloro-N-(2,5-dichlorophenyl)-N-[(R)-1-methyl(2-iodoethyl)]benzeneSulfonamide

To a solution of 4chloro-N-2,5-dichlorophenyl)-N-[(R)-1-methyl(2-hydroxyethyl)benzene-sulfonamide(0.660 g, 1.67 mmol), triphenylphosphine (0.530 g, 2.00 mmol) andimidazole (0.136 g, 2.00 mmol) in diethyl ether/CH₃CN(2:1, 3.0 mL) wasadded iodine (0.430 g, 1.67 mol) at 0° C. under nitrogen and stirred for12 hr. This mixture was concentrated under reduced pressure and dilutedwith CH₂Cl₂. This solution was washed with water (50 ml), dried overNa₂SO₄ and filtered. The organic solution was concentrated to afford thetitle compound as a light yellow oil in 96% yield.

EXAMPLE 25 (S)-4-triphenylmethylyloxy-2-butanol

To a solution of (S)+}1,3-butanediol (10.0 g, 0.110 mol), was addedtriphenylmethylchloride (33.0 g, 0.330 mol), 4-dimethylaminopyridine(1.40 g, 11.5 mmol) in CH₂Cl/pyridine (1:1, 500 mL).

Stirring was continued over 48 h. The solvent was removed, the mixturewas diluted with ether, washed with brine and dried over Na₂SO₄. Theorganic solution was filtered and concentrated. Silica gelchromatography with (5% ethyl acetate/hexanes) produced a clear oil (24g) in 70% yield.

EXAMPLE 264-Chloro-N-(2,5-dichlorophenyl]-N-[1(R)-methyl-(3-triphenylmethyloxy)-propyl]benezenesulfonamide

To a solution of 4-chloro-N-(2,5-dichlorophenyl)benzenesulfonamide (7.00g, 20.8 mmol), triphenylphosphine (7.00 g, 27.0 mmol),(S)-4-triphenylmethyloxy-2-butanol (8.60 g, 27.0 mmol) in THF (30 mL)was added diisopropylazodicarboxylate (5.48 g, 27.0 mmol) dropwise at 0°C. under nitrogen atmosphere. The resulting mixture was allowed to warmto 22° C. with stirring. After 18 h the mixture was washed with water,brine, dried over Na₂SO₄ and filtered. Silica gel chromatography (1:10ethyl acetate/hexanes) of the concentrate produced the title compound in90% yield.

EXAMPLE 274-Chloro-N-(2,5-dichlorophenyl)-N-[1(R)-methyl-(3-hydroxy)-propyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-dichlorophenyl)-N-[1(R)-methyl-(3-triphenylmethyloxy)-propyl)benzenesulfonamide(2.00 g, 3.00 mmol) in CH₃CN (20 mL) was added Amberlyst 15 ion-exchangeresin (6.0 g). The resulting mixture was allowed to stir at 22° C. for12 h and filtered. Silica gel chromatography (1:1 ethyl acetate:hexanes)of the concentrate afforded the title compound as a colorless oil inquantitative yield.

EXAMPLE 284-Chloro-N-(2,5-dichlorophenyl)-N-[1(R)methyl-(3-iodo)-propyl]benzeneSulfonamide

To a solution of4-chloro-N-(2,5-dichlorophenyl)-N-[1(R)-methyl-(3-hydroxy)-propyl]benzene-sulfonamide(1.40 g, 3.40 mmol), triphenylphosphine (0.900 g, 3.40 mmol) andimidazole (0.230 g, 3.40 mmol) in diethyl ether/CH₃CN (2:1, 7.0 mL) wasadded iodine (0.860 g, 3.40 mmol) at 0° C. under nitrogen and stirredfor 12 h. The solvent was removed, the residue was taken into CH₂Cl₂,washed with water, dried over Na₂SO₄ and filtered. The organic solutionwas concentrated to afford the title compound as a light yellow oil in96% yield.

EXAMPLE 294-Chloro-N-(2,5-dichlorophenyl)-N-[(R)-1-methyl-3-azidopropyl]]benzenesulfonamide

To a solution of4-chloro-N-(2,5-dichlorophenyl)-N-[(R)-1-methyl-3-bromopropylbenzene-sulfonamide(1.188 g, 2.295 mmol) in THF/H₂O (20/4, 24 mL) was added sodium azide(1.49 g, 22.9 mmol) at 22° C. The resulting mixture was allowed to stirat 22° C. for 4 days. The mixture was extracted with ether (3×60 mL).The combined organic extracts were washed with sat. NaHCO₃, dried overMgSO₄, filtered, and concentrated under reduced pressure. Silica gelchromatography (1:9 ethyl acetate:hexanes) of the concentrate afforded0.941 g of4-chloro-N-(2,5-dichlorophenyl)-N-[(R)-1-methyl-3-azidopropyl]]benzenesulfonamideas a colorless oil in 94% yield.

EXAMPLE 304-Chloro-N-(2,5-dichlorophenyl)-N-[(R)-1-methyl-3-aminopropyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-dichlorophenyl)-N-[(R)-1-methyl-3-azidopropyl]benzenesulfonamide(0.941 g, 2.16 mmol) in THF (21 mL) was added lithium aluminum hydride(4.33 mL, 1 M in THF) at 0° C. under nitrogen atmosphere. The resultingmixture was allowed to stir at 0° C. for 1 h and subsequently treated bysuccessive dropwise addition of 0.165 mL of water, 0.165 mL of 15%sodium hydroxide solution, and 0.493 mL of water. The mixture wasfiltered and concentrated under reduced pressure. Silica gelchromatography (3:10 ethyl acetate:hexanes) of the concentrate afforded0.748 g of4-chloro-N-2,5-dichlorophenyl)-N-[(R)-1-methyl-3-aminopropyl]benzenesulfonamideas a light brown oil in 85% yield.

EXAMPLE 31 (3S)-(1,1-dimethylethyl)dimethylsiloxy Butanal

A solution of methyl (S)-3-tert-butyldimethylsiloxy butyrate (35.0 g 151mmol) in hexane (400 mL) was cooled to −78° C. DIBAL-H (195 mL, 195mmol, 1M in hexanes) was added dropwise. Stirring was continued for 1 hafter which time water (75 mL) was cautiously added dropwise, afteraddition was complete stirring was continued at 22° C. for 18 h. Thereaction was diluted with diethyl ether and then decanted several times.The solvents were removed to afford(3S)-(1,1-dimethylethyl)dimethylsiloxy butanal as a clear oil inquantitative yield. ¹H NMR (CDCl₃) δ9.85 (s br, 1H), 4.40-4.51 (m, 1H),2.42-2.65 (m, 2H), 1.29 (d, 3H, J=6.0 Hz), 0.96 (s, 9H), 0.14 (d, 6H,J=3 Hz).

EXAMPLE 32(Trans)1,1-dimethylethyl-(5S)-(1,1-dimethylethyl)dimethylsiloxy-hex-2-enoate,

To a solution of (3S)-(1,1-dimethylethyl)dimethylsiloxy butanal (24.0 g121 mmol), in dichloromethane (400 mL) at 0° C. was added tert-butoxycarbonylmethylene triphenylphosphorane (50.0 g, 133 mmol). Stirring wascontinued for 2 h after which time the reaction was concentrated and theresulting oil was purified by silica gel chromatography (5% ethylacetate/Hexane) to afford(trans)1,1-dimethylethyl-(5S)-(1,1-dimethylethyl)dimethylsiloxy-hex-2-enoateas a clear oil in 93% yield. ¹H NMR (CDCl₃) δ6.79-6.90 (m, 1H) 5.75 (m1H, J=15.6 Hz), 3.85-3.87 (m, 1H), 226-2.32 (m, 2H), 1.47 (s, 9H), 1.15(d, 3H, J=6.0 Hz), 0.90 (s, 9H), 0.06 (s, 6H).

EXAMPLE 331,1-dimethylethyl-butyl-(5S)-(1,1-dimethylethyl)dimethylsiloxy-hexanoate,

A suspension of(trans)tert-butyl-(5S)-tert-butyldimethylsiloxy-hex-2-enoate (33.5 g,111 mmol), 10% Pd/C (5 g), in ethanol (250 mL), was hydrogenated at 45psi for 1 h. The catalyst was filtered off and the filtrate wasconcentrated to afford1,1-dimethylethyl-butyl-(5S)-(1,1-dimethylethyl)dimethylsiloxy-hexanoateas a white wax in quantitative yield. ¹H NMR (CDCl₁) 83.72-3.84 (m, 1H),2.20 (t, 2H, J=7.0 Hz), 1.60-1.74 (m, 2H), 1.35-1.70 (m, 4H), 1.44 (s,9H), 1.35 (d, 3H, J=6.0 Hz), 0.88 (s, 9H), 0.10 (s, 6H).

EXAMPLE 34 1,1-Dimethylethyl (5S)-5-hydroxyhexanoate

A solution of1,1-dimethylethyl-(5S)-(1,1-dimethylethyl)dimethylsiloxy-hexanoate (19.0g, 63.0 mmol) in THF (250 mL) was treated with tetrabutylammoniumfluoride (94 mL, 94 mmol, 1M in THF) at 0° C. The reaction mixture wasallowed to warm to 22° C., and stirring was continued for 18 h. Thereaction mixture was diluted with diethyl ether, washed with water, anddried over MgSO₄. Silica gel chromatography (20% ethyl acetate/hexane)of the concentrate produced 1 μl-dimethylethyl (5S)-5-hydroxyhexanoatein 89% yield. ¹H NMR (CDCl₃) δ3.74-3.86 (m, 1H), 2.32 (t, 2H, J=6.6 Hz),1.60-1.74 (m, 2H), 1.57 (s, 1H, OH), 1.44-1.48 (m, 2H), 1.45 (s, 9H),1.20 (d, 3H, J=6.0 Hz).

EXAMPLE 351,1-dimethylethyl(5R)-5-[(2,5-dichlorophenyl)-[(4-chlorophenyl)sulfonyl]-amino]hexanoate

To a solution 2,5-dichloro-N[[(4-chlorophenyl)]amino]phenyl)sulfonamide(2.42 g, 7.20 mmol), triphenyl phosphine (3.70 g, 14.4 mmol) and1,1-dimethylethyl(5S)-5-hydroxyhexanoate (2.70 g, 14.4 mmol) in THF (100mL) was added diisopropylazodicarboxylate (2.51 g, 14.4 mmol) dropwiseat 0° C. under nitrogen. The reaction mixture was allowed to warm to 22°C. with stirring for a period of 18 h. The reaction mixture was dilutedwith ethyl acetate then washed with water, brine and dried over MgSO₄.Silica gel chromatography (20% ethyl acetate/hexane) of the concentrateproduced1,1-dimethylethyl(5R)-5-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]-amino]hexanoatein 60% yield.

EXAMPLE 36(5R)-5-[(2,5-dichlorophenyl][(4-chlorophenyl)sulfonyl]-amino]hexanoicAcid

1,1-dimethylethyl(5R)-5-[(2,5-dichlorophenyl)-[(4-chlorophenyl)sulfonyl]-amino]hexanoate(700 g, 1.40 mmol) was treated with a 50% solution of trifluoroaceticacid in dichloromethane (20 mL). After 3 h the reaction was diluted withdichloromethane then washed with water, brine and dried over MgSO₄.Concentration under reduced pressure afforded(5R)-5-[(2,5-dichlorophenyl][(4-chlorophenyl)sulfonyl]-amino]hexanoicacid in quantitiative yield. MS (ESI), (M−H⁻) 450.IR-2975,1706,1466,1348.

EXAMPLE 374-Chloro-N(2,5-dichlorophenyl)-N-[5-(1R)-methyl-5-oxo-(4-thiomorpholinyl)pentyl]benzenesulfonamide

To a solution of(5R)-5-[(2,5-dichlorophenyl][(4-chlorophenyl)sulfonyl]-amino]hexanoicacid (2.00 g, 4.40 mmol), N,N-diisopropylethylamine (1.62 mL, 8.80 mmol)and 1-hydroxybenzotriazole (645 mg, 4.80 mmol), in dichloromethane (100mL) was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimidehydrochloride (920 mg, 4.80 mmol). After 18 h the solvent is removed andthe residue is taken into ethyl acetate and successively washed withaqueous HCl, water, brine and then concentrated to afford the titlecompound as a white solid (1.43 g) in 61% yield. MS (ESI), (MHz) 537.2.IR-2910,1643,1581,1466,1348.

EXAMPLE 384-Chloro-N(2,5-dichlorophenyl)-N-[5-(1R)-methyl-5-oxo-(1,1-dioxido-4-thiomorpholinyl)pentyl]benzenesulfonamide

A solution of4-chloro-N(2,5-dichlorophenyl)-N-[5-(1R)-methyl-5-oxo-(4-thiomorpholinyl)-pentyl]benzenesulfonamide(1.10 g, 2.10 mmol) in dichloromethane (100 mL) was treated with3-chloroperoxybenzoic acid (1.10 g, 5.10 mmol) at 0° C. After stirringfor 1 h the ice bath was removed and stirring was continued for 18 h.The reaction mixture was diluted with dichloromethane, and washed with1N NaOH, H₂O, brine, and dried over MgSO₄. Concentration produced thetitle compound (1.01 g) in 91% yield. MS (ESI), (M+H)³⁰ 569.2.IR-3441,2935,1653,1467,1428,1318.

EXAMPLE 394-Chloro-N-[5-chloro-2-fluorophenyl]-N-[(R)-1-methyl-4-[(1,1-dimethylethyl)dimethylsilyl]oxy)butyl]benzenesulfonamide

To a solution of 4-chloro-N-[5-chloro-2-fluorophenyl]benzenesulfonamide(500 mg, 1.56 mmol), triphenylphosphine (859 mg, 3.28 mmol) and5S-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-2-pentanol (682 mg, 3.12mmol) in THF (7 mL) was added diisopropylazodicarboxylate (0.645 mL,3.28 mol) dropwise at 0° C. under nitrogen. The resulting mixture wasallowed to warm to 22° C. with stirring. Stirring was continued for aperiod of 12 h followed by the addition of 15 mL of H₂O. The mixture wasextracted with ether (3×15 mL). The combined organic extracts werewashed with NaHCO₃ and sat. brine. The organic phase was dried overNa₂SO₄, filtered, and concentrated under reduced pressure. Silica gelchromatography (1:5 ethyl acetate:hexanes) of the concentrate afforded495 mg of4-chloro-N-[5-chloro-2-fluorophenyl]-N-[(R)-1-methyl-4-[(1,1-dimethylethyl)-dimethylsilyl]oxy)butyl]benzenesulfonamideas a yellow oil in 61% yield.

EXAMPLE 404-Chloro-N-[5-chloro-2-fluorophenyl]-N-[(R)-1-methyl-4-hydroxybutyl]benzenesulfonamide

To a solution of4-chloro-N-[5-chloro-2-fluorophenyl]-N-[(R)-1-methyl-4-[(1,1-dimethylethyl)-dimethylsilyl]oxy)butyl]benzenesulfonamide(495 mg, 0.951 mmol) in acetonitrile (4 mL) was added 48% aqueous HF (2n-LL) dropwise at 0° C. The resulting solution was stirred for 1 h at 0°C. followed by addition of 10 mL of 1M NaHCO₃. The product was extractedwith ether (2×25 mL), dried over Na₂SO₄, filtered, and concentratedunder reduced pressure. Silica gel chromatography (ethyl acetate) of theconcentrate afforded 336 mg of4-chloro-N-[S-chloro-2-fluorophenyl]-N-[(R)-1-methyl-4-hydroxybutyl]benzenesulfonamideas a yellow oil in 87% yield.

EXAMPLE 414-Chloro-N-[5-chloro-2-fluorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamide

To a solution of4-chloro-N-[5-chloro-2-fluorophenyl]-N-[(R)-1-methyl-4-hydroxybutyl]-benzenesulfonamide(336 mg, 0.827 mmol) in acetonitrile (4 mL) was added triphenylphosphine(433 mg, 1.65 mmol) and carbon tetrabromide (548 mg, 1.65 mmol) at 0° C.The resulting mixture was allowed to stir at 22° C. for 12 h followed bythe addition of 25 mL of sat. ammonium chloride. The product wasextracted with ether (2×25 mL), dried over Na₂SO₄, filtered, andconcentrated under reduced pressure. Silica gel chromatography (1:4ethyl acetate:hexanes) of the concentrate afforded 349 mg of4-chloro-N-[5-chloro-2-fluorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamideas a yellow oil in 88% yield.

EXAMPLE 42(4R)-4-[N-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]pentylsulfonicAcid

(4R)-4-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]pentylsulfonicacid was prepared analogous to (4R)-4-[2,5dichlorophenyl][4-chlorophenyl)sulfonyl]-amine]pentylsulfonic acid byreacting4-chloro-N-[5-chloro-2-fluorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith Na₂SO₃. Yield=86%; MS (ESI) 470 (M+1).

EXAMPLE 43(4R)-4-[N-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]pentylsulfonylChloride

(4R)-4-[N-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]pentylsulfonylchloride was prepared analogous to(4R)-4-[N-[2,5-dichlororophenyl][(4-chlorophenyl)sulfonyl]amino]pentyl-sulfonylchloride by reacting(4R)-4-[N-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]-pentylsulfonicacid with phosphorus pentachloride: Yield=81%; MS (ESI) 489 (+1).

EXAMPLE 444-Chloro-N-(5-chloro-2-fluorophenyl)-4-azidobutyl]benzenesulfonamide

To a solution of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl-4-bromobutyl]-benzenesulfonamide(0.343 g, 0.730 mmol) in THF/H₂O (8/2 mL) was added sodium azide (0.237g, 7.30 mmol) at 22° C. The resulting mixture was allowed to stir at 22°C. for 10 days. The mixture was extracted with ether (3×20 mL). Thecombined organic extracts were washed with sat. NaHCO₃, dried overMgSO₄, filtered, and concentrated under reduced pressure. Silica gelchromatography (1:9 ethyl acetate:hexanes) of the concentrate afforded0.227 g of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl-4-azidobutyl]benzenesulfonamideas a colorless oil in 72% yield.

EXAMPLE 454-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl-4-aminobutyl]benzenesulfonamide

To a solution of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl]4-azidobutyl]-benzenesulfonamide(0.325 g, 7.77 mmol) in THF (7 mL) was added lithium aluminum hydride(1.55 mL, 1 M in THF) at 0° C. under nitrogen atmosphere. The resultingmixture was allowed to stir at 0° C. for 1 h and subsequently treated bysuccessive dropwise addition of 0.060 mL of water, 0.060 ml of 15%sodium hydroxide solution, and 0.180 mL of water. The mixture wasfiltered and concentrated under reduced pressure. Silica gelchromatography (3:10 ethyl acetate:hexanes) of the concentrate afforded0.207 g of the title compound as a light brown oil in 91% yield.

EXAMPLE 464-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl-3-azidopropyl]benzenesulfonamide

To a solution of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl-3-bromopropyl]benzenesulfonamide(1.64 g, 3.27 mmol) in THF/H₂O (20/4, 24 mL) was added sodium azide(2.13 g, 32.7 mmol) at 22° C. The resulting mixture was allowed to stirat 22° C. for 4 days. The mixture was extracted with ether (3×60 mL).The combined organic extracts were washed with sat. NaHCO₃, dried overMgSO₄, filtered, and concentrated under reduced pressure. Silica gelchromatography (1:9 ethyl acetate:hexanes) of the concentrate afforded1.38 g of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl-3-azidopropyl]benzenesulfonamideas a colorless oil in 95% yield.

EXAMPLE 474-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl-3-aminopropyl]benzenesulfonamide

To a solution of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl-3-azidopropyl]-benzenesulfonamide(1.34 g, 3.27 mmol) in THF (32 mL) was added lithium aluminum hydride(6.53 mL, 1 M in THF) at 0° C. under nitrogen atmosphere. The resultingmixture was allowed to stir at 0° C. for 1 h and subsequently treated bysuccessive dropwise addition of 0.248 mL of water, 0.248 mL of 15%sodium hydroxide solution, and 0.744 mL of water. The mixture wasfiltered and concentrated under reduced pressure. Silica gelchromatography (3:10 ethyl acetate:hexanes) of the concentrate afforded1.12 g of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl-3-aminopropyl]benzenesulfonamideas a light brown oil in 85% yield.

EXAMPLE 484-Chloro-N-[5-fluoro-2-flurophenyl]-N-[(R)-1-methyl-4-[(1,1-dimethylethyl)dimethylsilyl]oxy)butyl]benzenesulfonamide

To a solution of 4-chloro-N-[5-fluoro-2-fluorophenyl]benzenesulfonamide(500 mg, 1.65 mmol), triphenylphosphine (909 mg, 3.47 mmol) and5S-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-2-pentanol (719 mg, 3.30mmol) in THF (7 mL) was added diisopropylazodicarboxylate (0.682 mL,3.47 mol) dropwise at 0° C. under nitrogen. The resulting mixture wasallowed to warm to 22° C. with stirring. Stirring was continued for aperiod of 12 h followed by the addition of 15 mL of H₂O. The mixture wasextracted with ether (3×15 mL). The combined organic extracts werewashed with NaHCO₃ and sat. brine. The organic phase was dried overNa₂SO₄, filtered, and concentrated under reduced pressure. Silica gelchromatography (1:5 ethyl acetate:hexanes) of the concentrate afforded466 mg of4-chloro-N-[5-fluoro-2-flurophenyl]-N-[(R)-1-methyl-4-[(1,1-dimethylethyl)-dimethylsilyl]oxy)butyl]benzene-sulfonamideas a yellow oil in 56% yield.

EXAMPLE 494-Chloro-N-[5-fluoro-2-flurophenyl]-N-[(R)-1-methyl-4-hydroxybutyl]benzenesulfonamide

To a solution of4-chloro-N-[5-fluoro-2-flurophenyl]-N-[(R)-1-methyl-4-[(1,1-dimethylethyl)-dimethylsilyl]oxy)butyl]benzenesulfonamide(466 mg, 0.924 mmol) in acetonitrile (4 mL) was added 48% aqueous HF (2mL) dropwise at 0° C. The resulting solution was stirred for 1 h at 0°C. followed by addition of 10 ml of 1M NaHCO₃. The product was extractedwith ether (2×25 mL), dried over Na₂SO₄, filtered, and concentratedunder reduced pressure. Silica gel chromatography (ethyl acetate) of theconcentrate afforded 317 mg of4-chloro-N-[5-fluoro-2-flurophenyl]-N-[(R)-1-methyl-4-hydroxybutyl]benzenesulfonamideas a yellow oil in 88% yield.

EXAMPLE 504-Chloro-N-[5-fluoro-2-flurophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamide

To a solution of4-chloro-N-[5-fluoro-2-flurophenyl]-N-[(R)-1-methyl-4-hydroxybutyl]-benzenesulfonamide(317 mg, 0.813 mmol) in acetonitrile (4 mL) was added triphenylphosphine(425 mg, 1.62 mmol) and carbon tetrabromide (537 mg, 1.62 mmol) at 0° C.The resulting mixture was allowed to stir at 22° C. for 12 h followed bythe addition of 25 mL of sat. ammonium chloride. The product wasextracted with ether (2×25 mL), dried over Na₂SO₄, filtered, andconcentrated under reduced pressure. Silica gel chromatography (1:4ethyl acetate:hexanes) of the concentrate afforded 323 mg of4-chloro-N-[5-fluoro-2-flurophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamideas a yellow oil in 86% yield.

EXAMPLE 51(4R)-4-[N-[2,5-difluorophenyl][(4-chlorophenyl)sulfonyl]amino]pentylsulfonicAcid

(4R)-4-[N-[2,5-difluorophenyl][(4-chlorophenyl)sulfonyl]amino]pentylsulfonicacid was prepared analogous to(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amine]pentylsulfonicacid by reacting4-chloro-N-[2,5-difluorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benznesulfonamidewith Na₂SO₃. Yield=84%; MS (ESI) 453 (M+1).

EXAMPLE 52(4R)-4-[N-[2,5-difluorophenyl][(4-chlorophenyl)sulfonyl]amino]pentylsulfonylchloride

(4R)-4-[N-[2,5-difluorophenyl][(4-chlorophenyl)sulfonyl]amino]pentylsulfonylchloride was prepared analogous to(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride by reacting(4R)-4-[N-[2,5-difluorophenyl][(4-chlorophenyl)sulfonyl]amino]pentylsulfonicacid with phosphorus pentachloride. Yield=88%; MS (ESI) 434 (M+1).

EXAMPLE 534-Chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-4-azidobutyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-4-bromobutyl]-benzenesulfonamide(0.505 g, 1.12 mmol) in THF/H₂O (8/2, 10 mL) was added sodium azide(0.363 g, 5.58 mmol) at 22° C. The resulting mixture was allowed to stirat 22° C. for 10 days. The mixture was extracted with ether (3×20 mL).The combined organic extracts were washed with sat. NaHCO₃, dried overMgSO₄, filtered, and concentrated under reduced pressure. Silica gelchromatography (1:9 ethyl acetate:hexanes) of the concentrate afforded0.455 g of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-4-azidobutyl]benzenesulfonamideas a colorless oil in 98% yield.

EXAMPLE 544-Chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-4-aminobutyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-4-azidobutyl]benzene-sulfonamide(0.394 g, 0.949 mmol) in THF (10 mL) was added lithium aluminum hydride(1.90 mL, 1 M in THF) at 0° C. under nitrogen atmosphere. The resultingmixture was allowed to stir at 0° C. for 1 h and subsequently treated bysuccessive dropwise addition of 0.072 mL of water, 0.072 mL of 15%sodium hydroxide solution, and 0.216 mL of water. The mixture wasfiltered and concentrated under reduced pressure. Silica gelchromatography (3:10 ethyl acetate:hexanes) of the concentrate afforded0.329 g of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-4-aminobutyl]benzenesulfonamideas a light brown oil in 89% yield.

EXAMPLE 554-Chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-3-azidopropyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-3-bromopropyl]-benzenesulfonamide(1.74 g, 3.58 mmol) in THF/H₂O (20/4, 24 mL) was added sodium azide(2.33 g, 35.8 mmol) at 22° C. The resulting mixture was allowed to stirat 22° C. for 4 days. The mixture was extracted with ether (3×60 mL).The combined organic extracts were washed with sat. NaHCO₃, dried overMgSO₄, filtered, and concentrated under reduced pressure. Silica gelchromatography (1:9 ethyl acetate:hexanes) of the concentrate afforded1.53 g of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-3-azidopropyl]benzenesulfonamideas a colorless oil in 95% yield.

EXAMPLE 564-Chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-3-aminopropyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-3-azidopropyl]benzenesulfonamide(0.144 g, 3.59 mmol) in THF (35 mL) was added lithium aluminum hydride(7.16 mL, 1 M in THF) at 0° C. under nitrogen atmosphere. The resultingmixture was allowed to stir at 0° C. for 1 h w and subsequently treatedby successive dropwise addition of 0.272 mL of water, 0.272 mL of 15%sodium hydroxide solution, and 0.816 mL of water. The mixture wasconcentrated under reduced pressure. Silica gel chromatography (3:10ethyl acetate:hexanes) of the concentrate afforded 1.12 g of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-3-aminopropyl]benzenesulfonamideas a light brown oil in 97% yield.

EXAMPLE 574-Chloro-N(2,5-dichlorophenyl)-N-(5-(1.1-dioxido-4-thiomorpholinyl)-1(R)-methylpentyl)benzenesulfonamide

A solution of4-chloro-N(2,5-dichlorophenyl)-N-[5-(1R)-methyl-5-oxo-(1.1-dioxido-4-thiomorpholinyl)pentyl]benzenesulfonamide(700 mg, 1.20 mmol) in THF (45 mL) was treated with a solution ofborane-methyl sulfide complex (2M in THF, 1.8 mL, 3.6 mmol) dropwise atroom temperature. After stirring for 18 h the reaction was cooled to 0°C. and quenched with methanol (50 mL), followed by treatment with HClgas. The solvents were removed and the material was then purified byflash chromatography (silica gel, 15% ethyl acetate/hexane) to affordthe title compound (300 mg) as a white solid in 50% yield. MS (ESI),(M+H)+553.0. IR-3430,2933,1467,1348,1326.

EXAMPLE 58 N-cyclopropylmethyl-3-(1H)-imidazolylpropylamine

1-(3-aminopropyl)imidazole (Aldrich, 10.0 g, 0.0799 moles) was dissolvedin CH₂Cl₂ (100 mL) along with pyridine (7.57 g, 0.0959 moles, 1.2 eq.).Cyclopropanecarbonyl chloride (Aldrich, 8.76 g, 0.0839 moles, 1.05 eq.)was added dropwise and the mixture was stirred for 18 hours. The solventwas removed and the crude mixture was chromatographed over silica gelusing 5-10% methanol in CH₂Cl₂ with 0.5% NH₄OH, give the amide (14.3 g,93%). The purified amide intermediate (14.3 g, 0.074 moles) wasdissolved in THF (300 mL). Lithium aluminum hydride (0.148 moles, 148 mLof 1M soln. in THF, 2.0 eq.) was added and the mixture was refluxed for3 days. The mixture was carefully quenched with 1N NaOH (10 mL) andrefluxed for three hours. The hot solution was filtered over celite, andthe solvent was removed to give pureN-cyclopropylmethyl-3-(1H)-imidazolylpropylamine (7.57 g, 57%) as aviscous yellow oil. NMR (CDCl₃); 0.09 (m, 2H); 0.46 (m, 2H); 0.90 (m,1H); 1.89 (quintet, J=6.9 Hz, 2H); 2.43 (d, J=6.9 Hz, 2H); 2.61 (t,J=6.8 Hz, 2H); 4.05 (t, J=6.9 Hz, 2H); 6.92 (s, 1H); 7.05 (s, 1H); 7.48(s, 1H).

EXAMPLE 594-Chloro-N-(2,5-dichlorophenyl)-N-[3-[(N′-cyclopropylmethyl)-N′(3-(1H)-imidazolylpropyl)]-[(R)-methylpropylcarboxamido]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-(3-(carboxy)-1(R)-methylpropyl)benzenesulfonamide(405 mg, 0.928 mmoles) was dissolved in THF (10 mL) and CH₂Cl₂ (15 mL).N-Cyclopropylmethyl-3-(1H)-imidazolylpropylamine (166 mg, 0.928 mmoles)was added along with 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimidehydrochloride (230 mg, 0.0012 moles, 1.3 eq.) and Hunig's base (I drop).The mixture was stirred at room temperature for 18 hours and thesolvents were removed. The residue was dissolved in CH₂Cl₂, washed withsat. NaHCO₃, and brine. The organic layer was dried over Na₂SO₄ andevaporated. Chromatography over silica gel using 2-10% methanol inCH₂Cl₂ with 0.5% NH₄OH gave4-chloro-N-(2,5-dichlorophenyl)-N-[3-[(N′-cyclopropylmethyl)-N′(3-(1H)-imidazolylpropyl)]-1(R)-methylpropylcarboxamido]benzenesulfonamide(370 mg, 67%). Yellow viscous oil: IR (neat, CH₂Cl₂) 1637, 1467, 1348,1166, 1095, 622 cm⁻¹; MS (ESI+), 599 (M+H)⁺.

EXAMPLE 604-Chloro-N-(2,5-dichlorophenyl)-N-[4-(N′-cyclopropylmethyl)-N′(3-(1H)-imidazolylpropylamino)-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-(4-(N-cyclopropylmethyl-N-3-(1H)-imidazolylpropyl)-1(R)-methylbutylcarboxamide)benzenesulfonamide(1.00 g, 1.67 mmoles) was dissolved in THF (50 mL). Borane dimethylsulfide (2.51 moles, 1.25 mL of a 2.0M solution in toluene, 1.5 eq.) wasadded and the mixture was refluxed for 6 hours, then allowed to stir atroom temperature for 18 hours. The mixture was slowly quenched withmethanol (5 mL), and 1N HCl (5 mL). The solvent was removed, the residuewas dissolved in CH₂Cl₂ and washed with 1N NaOH, then brine. Prep HPLC(Reverse phase, methanol/H₂O/0.1% trifluoroacetic acid) gave a smallamount of pure product (75.2 mg, 8%). Yield=8%; Colorless viscous oil:IR (neat, CH₂Cl₂) 1467, 1350, 1167, 1094, 753, 622 cm⁻¹; MS (ESI+), 583(M+H)⁺.

EXAMPLE 612-(Methylsulfonylmethyl)piperidine1)2-methylsulfonylmethyl)pyridine

Picolyl chloride hydrochloride (15.9 g, 0.0967 moles) was dissolved inDMF (70 mL) and methanesulfinic acid sodium salt (10.9 g, 0.106 moles,1.1 eq.) was added along with triethylamine (10.7 g, 0.106 moles, 1.1eq.). The mixture was refluxed for 1 hour. The DMF was removed, theresidue dissolved in CH₂Cl₂, washed with sat. Na₂CO₃, and brine. Theorganic layer was dried over Na₂SO₄ and evaporated to give crudeproduct. Purification was performed over silica gel using 20-100% ethylacetate/hexane to give a yellow oil which solidified on standing (4.50g, 27%).

EXAMPLE 62 (2) 2-(Methylsulfonylmethyl)piperidine

2-(Methylsulfonylmethyl)pyridine (4.40 g, 0.0257 moles) and PtO₂ (0.50g) were suspended in ethanol (80 mL) with 1N HCl (15 mL). The mixturewas hydrogenated at 50 psi for 18 hours. The catalyst was filtered andthe solvent removed. The residue was dissolved in CH₂Cl₂ and washed withsat. Na₂CO₃. The aqueous layer was extracted with CH₂Cl₂ (3×25 mL). Theorganic layers were combined and dried over Na₂SO₄ and evaporated togive a yellow oil (4.11 g, 90%) which solidified on standing. Furtherpurification was unnecessary. LCMS (178, M+H).

EXAMPLE 63 4-(Methylsulfonylmethyl)piperidine

To a stirred solution of 4-(hydroxymethyl)piperidine (6.00 g, 52.0 mmol)in 100 mL of CH₂Cl₂ was added di-tert-butyl dicarbonate (12.52 g, 57.0mmol) at 0° C. and stirred for 1 h. The reaction mixture was warmed toroom temperature over a period of 1 h. The solvents were removed and thesolid was diluted with 250 mL of ethyl acetate, washed with 1M NaOH (200mL), brine (200 mL), and and dried over Na₂SO₄. The solvent wasevaporated to afford an oil.

The resulting oil was dissolved in toluene (300 mL) andtriphenylphosphine (14 g, 55 mmol), iodine (14 g, 55 mmol), andimidazole (4.3 g, 63 mmol) were added. The reaction mixture was stirredat room temperature for 1 h and the solvent was removed. The crudeproduct was passed through silica gel using 10% ethyl acetate in hexanesas the eluent to yield an oil after concentration of the desiredfractions.

The resulting oil was dissolved in THF (100 mL) and sodium thiomethoxide(1.20 g, 16.0 mmol) was added at room temperature. The reaction mixturewas stirred for 12 h and then diluted with ethyl acetate (100 mL),washed with water (200 mL), and dried over Na₂SO₄. The solvents wereremoved to afford an oil.

The resulting oil was dissolved in CH₂Cl₂ and 3-chloroperoxybenzoic acid(5.90 g, 34.0 mmol) at room temperature and allowed to stir overnight.The reaction mixture was washed with 1N NaOH (50 mL), and dried overNa₂SO₄. The crude sulfone was purified using silica gel chromatography(ethyl acetate) to yield the title compound as an oil in 41% overallyield.

EXAMPLE 64 3-(Methylsulfonylmethyl)piperidine

To a stirred solution of 3-(hydroxymethyl)piperidine (4.43 g, 35.0 mmol)and pyridine (14.2 mL) in 100 mL of CH₂Cl₂ was added benzoyl chloride(4.06 mL, 35.0 mmol) at 0° C. and stirred for 18 h. This mixture waswashed with 2M HCl (50 mL), dried over Na₂SO₄ and the solvent wasevaporated to afford an oil.

The resulting oil was dissolved in CH₂Cl₂ (70 mL), triethylamine (17.6mL), and methanesulfonyl chloride (5.74 mL, 70.0 mmol). The reactionmixture was stirred at room temperature for 12 h. This mixture waswashed with water (50 mL), dried over Na₂SO₄ and the solvent wasevaporated to afford an oil.

The resulting oil was dissolved in THF (70 mL) and sodium thiomethoxide(4.48 g, 64.2 mmol) was added at room temperature. The reaction mixturewas stirred for 12 h and then diluted with ethyl acetate (100 mL),washed with water (200 mL), and dried over Na₂SO₄. The solvents wereremoved to afford an oil.

The resulting oil was dissolved in CH₂Cl₂ (100 mL) and 80%3-chloroperoxybenzoic acid (20.1 g, 70.0 mmol) was added at roomtemperature and allowed to stir overnight. The reaction mixture waswashed with 1N NaOH (50 mL), and dried over Na₂SO₄. The crude sulfonewas purified using silica gel chromatography (ethyl acetate) to yield an4.69 g of an oil.

The resulting oil was suspended in 50 mL of 6N HCl and heated to 110° C.for 18 h. To the resulting solution was added 35 mL of 10N NaOH and themixture was extracted with ether (10×100 mL). After evaporation of thesolvent, the title compound was isolated as an oil in 30% overall yield.

EXAMPLE 65 4-(Sulfonylmethyl)piperidine

To a stirred solution of 4-(hydroxy)piperidine (3.89 g, 35.0 mmol) andpyridine (14.2 mL) in 100 mL of CH₂Cl₂ was added benzoyl chloride (4.06mL, 35.0 mmol) at 0° C. and stirred for 18 h. This mixture was washedwith 2M HCl (50 mL), dried over Na₂SO₄ and the solvent was evaporated toafford an oil.

The resulting oil was dissolved in CH₂Cl₂ (70 mL), triethylamine (17.6mL), and methanesulfonyl chloride (5.74 ml, 70.0 mmol). The reactionmixture was stirred at room temperature for 12 h. This mixture waswashed with water (50 mL), dried over Na₂SO₄ and the solvent wasevaporated to afford an oil.

The resulting oil was dissolved in THF (70 mL) and sodium thiomethoxide(4.48 g, 64.2 mmol) was added at room temperature. The reaction mixturewas stirred for 12 h and then diluted with ethyl acetate (100 mL),washed with water (200 mL), and dried over Na₂SO₄. The solvents wereremoved to afford an oil.

The resulting oil was dissolved in CH₂Cl₂ (100 mL) and 80%3-chloroperoxybezoic acid (20.1 g, 70.0 mmol) was added at roomtemperature and allowed to stir overnight. The reaction mixture waswashed with 1N NaOH (50 mL), and dried over Na₂SO₄. The crude sulfonewas purified using silica gel chromatography (ethyl acetate) to yield5.18 g of an oil.

The resulting oil was suspended in 50 mL of 6N HCl and heated to 110° C.for 18 h. To the resulting solution was added 35 mL of 10N NaOH and themixture was extracted with ether (10×100 mL). After evaporation of thesolvent, the title compound was isolated as an oil in 36% overall yield.

EXAMPLE 66 3-(Sulfonylmethyl)piperidine

To a stirred solution of 3-(hydroxy)piperidine hydrochloride (5.29 g,35.0 mmol) and pyridine (14.2 mL) in 100 mL of CH₂Cl₂ was added benzoylchloride (4.06 mL, 35.0 mmol) at 0° C. and stirred for 18 h. Thismixture was washed with 2M HCl (50 mL), dried over Na₂SO₄ and thesolvent was evaporated to afford an oil.

The resulting oil was dissolved in CH₂Cl₂ (70 mL), triethylamine (17.6mL), and methanesulfonyl chloride (5.74 mL, 70.0 mmol). The reactionmixture was stirred at room temperature for 12 h. This mixture waswashed with water (50 mL), dried over Na₂SO₄ and the solvent wasevaporated to afford an oil.

The resulting oil was dissolved in THF (70 mL) and sodium thiomethoxide(4.48 g, 64.2 mmol) was added at room temperature. The reaction mixturewas stirred for 12 h and then diluted with ethyl acetate (100 mL),washed with water (200 mL), and dried over Na₂SO₄. The solvents wereremoved to afford an oil.

The resulting oil was dissolved in CH₂Cl₂ (100 mL) and 80%3-chloroperoxybezoic acid (20.1 g, 70.0 mmol) was added at roomtemperature and allowed to stir overnight. The reaction mixture waswashed with 1N NaOH (50 mL), and dried over Na₂SO₄. The crude sulfonewas purified using silica gel chromatography (ethyl acetate) to yield5.20 g of an oil.

The resulting oil was suspended in 50 mL of 6N HCl and heated to 110° C.for 18 h. To the resulting solution was added 35 mL of 10N NaOH and themixture was extracted with ether (10×100 mL). After evaporation of thesolvent, the title compound was isolated as an oil in 38% overall yield.

EXAMPLE 67 (S)-3-(sulfonylmethyl)pyrrolidine

To a stirred solution of (R)-3-pyrrolidinol hydrochloride (4.76 g, 35.0mmol) and pyridine (14.2 mL) in 100 mL of CH₂Cl₂ was added benzoylchloride (4.06 mL, 35.0 mmol) at 0° C. and stirred for 18 h. Thismixture was washed with 2M HCl (50 mL), dried over Na₂SO₄ and thesolvent was evaporated to afford an oil.

The resulting oil was dissolved in CH₂Cl₂ (70 mL), triethylamine (17.6mL), and methanesulfonyl chloride (5.74 mL, 70.0 mmol). The reactionmixture was stirred at room temperature for 12 h. This mixture waswashed with water (50 mL), dried over Na₂SO₄ and the solvent wasevaporated to afford an oil.

The resulting oil was dissolved in THF (70 mL) and sodium thiomethoxide(4.48 g, 64.2 mmol) was added at room temperature. The reaction mixturewas stirred for 12 h and then diluted with ethyl acetate (100 mL),washed with water (200 mL), and dried over Na₂SO₄. The solvents wereremoved to afford an oil.

The resulting oil was dissolved in CH₂Cl₂ (100 mL) and 80%3-chloroperoxybenzoic acid (20.1 g, 70.0 mmol) at room temperature andallowed to stir overnight. The reaction mixture was washed with 1N NaOH(50 mL), and dried over Na₂SO₄. The crude sulfone was purified usingsilica gel chromatography (ethyl acetate) to yield 5.49 g of an oil.

The resulting oil was suspended in 50 mL of EN HCl and heated to 110° C.for 18 h. To the resulting solution was added 35 mL of 10N NaOH and themixture was extracted with ether (10×100 mL). After evaporation of thesolvent, the title compound was isolated as an oil in 39% overall yield.

EXAMPLE 68 (R)-2-methylsulfonyl)methyl)pyrrolidine

N-Benzoyl-(R)-2-(methylthio)methyl)pyrrolidine was prepared by themethod of Dieter and Tokles (J.A.C.S., 1987, 109, 2040-2046).

N-Benzoyl-(R)-(2-(methylthio)methyl)pyrrolidine (2.70 g, 0.0115 moles)was dissolved in CH₂Cl₂ (50 mL), cooled to 0° C., thenmeta-chloroperbenzoic acid (3.97 g, 0.0287 moles, 2.5 eq.) was addedover 10 min. The mixture was stirred at room temperature for 2 hours,diluted with CH₂Cl₂, and washed with brine. The organic layer was driedover Na₂SO₄ and evaporated to give crude product. Purification wasperformed over silica gel using 20-100% ethyl acetate/hexane to giveN-benzoyl-(R)-(2-(methylsulfonyl)methyl)pyrrolidine as a yellow solid(1.70 g, 0.00637 moles, 55%). LCMS (268, (M+H)).

N-Benzoyl-(R)(2-(methylsulfonyl)methyl)pyrrolidine (1.70 g, 0.00637moles) was dissolved in 2N HCl (20 mL) and refluxed for 48 hours. Themixture was cooled and neutralized with sat. K₂CO₃. The aqueous layerwas extracted using 50% ethyl acetate/t-BuOH, dried over MgSO₄, driedover Na₂SO₄ and evaporated to give(R)(2-(methylsulfonyl)methyl)pyrrolidine as a yellow oil (600 mg,0.00368 moles, 58%) which was used without further purification. LCMS(186, (M+23)).

The preparation of ester intermediates can be carried out according tothe general procedure described herein for coupling ofN-aryl-N-haloalkyl sulfonamides with amines, using commerciallyavailable methyl thiazolidine-2-carboxylate (Lancaster, CAS#50703-06-5). Methyl (R)-thiazolidine-4-carboxylate (CAS#65983-36-0) wasprepared from the acid following literature procedures.

EXAMPLE 694-Chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamide

To a solution of4-chloro-N-[2,5-dichlorophenyl]-N-1(R)-1-methyl-3-bromopropyl]benzenesulfonamide(0.375 mg, 0.795 mmol) in CH₃CN (20 mL), was added2-(methylsulfonyl-methyl)piperidine (0.282 g, 1.59 mmol), K₂CO₃ (500mg), and Hunigs base (2 drops). The mixture was refluxed for 2 days. Thesolvent was removed and the crude mixture was dissolved in CH₂Cl₂ andwashed with brine. The CH₂Cl₂ layer was dried over Na₂SO₄ and evaporatedto give crude product. Purification was performed over silica gel using10% methanol in CH₂Cl₂ with 0.5% NH₄OH to afford4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-(methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)-benzenesulfonamideas a yellow glassy olid in 80% yield. IR (KBr) 1468, 1349, 1296, 1167,1138, 1095, cm⁻¹; MS (ESI+), 567 (M+H)⁺.

EXAMPLE 704-Chloro-N-(2,5-dichlorophenyl)-N-[3-[[3-(methylthio)methyl]-1-piperidinyl]-1(R)-methylpropyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[3-[[3-(methylthio)methyl]-1-piperidinyl]-1(R)-methylpropyl]benzenesulfonamidewas prepared analogous to4-chloro-N-2,5-dichlorophenyl)-N-(3-(2-(methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-3-bromopropyl]benzenesulfonamidewith 3-(methyl-thiomethyl)piperidine. Yield=86%; MS (ESI+), 535 (M+H)⁺.

EXAMPLE 714-Chloro-N-(2,5-dichlorophenyl)-N-[3-[(3-(methylsulfonyl)methyl]-1-piperidinyl-1(R)-methylpropyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[3-[[3{methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylpropyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-3-bromopropyl]benzenesulfonamidewith 3-(methylsulfonylmethyl)piperidine. Yield=81%; MS (ESI+), 567(M+H)⁺.

EXAMPLE 724-Chloro-N-(2,5-dichlorophenyl)-N-[3-[(4-methylthio)-1-piperidinyl]-1(R)-methylpropyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[3-[(4-methylthio)-1-piperidinyl]-1(R)-methylpropyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-3-bromopropyl]benzenesulfonamidewith 4-(methylthio)-piperidine. Yield=88%; MS (ESI+), 521 (M+H)⁺.

EXAMPLE 734-Chloro-N-(2,5-dichlorophenyl)-N-[3-[(4-methylsulfonyl)-1-piperidinyl]-1(R)-methylpropyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[3-[(4-methylsulfonyl)-1-piperidinyl]-1(R)-methylpropyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-(methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-3-bromopropyl]benzenesulfonamidewith 4-(methylsulfonyl)-piperidine. Yield=9%; MS (ESI+), 553 (M+H)⁺.

EXAMPLE 744-Chloro-N-(2,5-dichlorophenyl)-N-[3-[(3-methylthio)-1-piperidinyl]-1(R)-methylpropyl]benzenesulfonamide

4-chloro-N-2,5-dichlorophenyl)-N-[3-[(3-methylthio)-1-piperidinyl]-1(R)-methylpropyl]-15benzenesulfonamide was prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-3-bromopropyl]benzenesulfonamidewith 3-(methylthio)-piperidine. Yield=85%; MS (ESI+), 521 (M+H)⁺.

EXAMPLE 754-Chloro-N-(2,5-dichlorophenyl)-N-[3-[(3-methylsulfonyl)-1-piperidinyl]-1(R)-methylpropyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[3-[(3-methylsulfonyl)-1-piperidinyl]-1(R)-methylpropyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-3-bromopropyl]benzenesulfonamidewith 3-(methylsulfonyl)-piperidine. Yield=90%; MS (ESI+), 553 (M+H)⁺.

EXAMPLE 764-Chloro-N-(2,5-dichlorophenyl)-N-[3-[(3-methylthio)-1-pyrrolidinyl]-1(R)-methylpropyl]benzenesulfonamide

4-chloro-N-2,5-dichlorophenyl)-N-[3-[(3-methylthio)-1-pyrrolidinyl]-2(R)-methylpropyl]benzenesulfonamide was prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methyl-sulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-3-bromopropyl]benzenesulfonamidewith 3-(methylthio)pyrrolidine. Yield=83%; MS (ESI+), 507 (M+H)⁺.

EXAMPLE 774-Chloro-N-2,5-dichlorophenyl)-N-[3-[(3-methylsulfonyl)-1-pyrrolidinyl]-1(R)-methylpropyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[3-[(3-methylsulfonyl)-1-pyrrolidinyl]-1(R)-methylpropyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-3-bromopropyl]benzenesulfonamidewith 3-(methylsulfonyl)-pyrrolidine. Yield=86%; MS (ESI+), 539 (M+H)⁺.

EXAMPLE 784-Chloro-N-(2,5-dichlorophenyl)-N-(4-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylbutyl)benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[2-(methylsulfonyl)methyl-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith 2-(methylsulfonylmethyl)piperidine. Yield=28%; yellow foam: IR(neat, CH₂Cl₂) 1467, 1296, 1166, 1138, 1095, 622, cm⁻¹; MS (ESI+), 581(M+H)⁺.

EXAMPLE 794-Chloro-N-(2,5-dichlorophenyl)-N-[4-[[4-methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-2,5-dichlorophenyl)-N-[4-[[4-methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith 4-(methylsulfonylmethyl)piperidine. Yield=60%; MS (ESI+), 581(M+H)⁺.

EXAMPLE 804-Chloro-N-(2,5-dichlorophenyl)-N-[4-[3-[(methylthio)methyl]-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[3-(methylthio)methyl]-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith 3-(methylthio-methyl)piperidine. Yield=91%; MS (ESI+), 549 (M+H)⁺.

EXAMPLE 814-Chloro-N-2,5-dichlorophenyl)-N-[3-[(methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[3-(methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith 3-(methylsulfonylmethyl)piperidine. Yield=77%; MS (ESI+), 581(M+H)⁺.

EXAMPLE 824-Chloro-N-(2,5-dichlorophenyl)-N-[4-[(4-methylthio)-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4-[(4-methylthio)-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith 4-(methylthio)-piperidine. Yield=88%; MS (ESI+), 535 (M+H)⁺.

EXAMPLE 834-Chloro-N-(2,5-dichlorophenyl)-N-[4-[(4-methylsulfonyl)-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4[(4-methylsulfonyl)-1-piperidinyl]-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl])—N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl]4-bromobutyl]benzenesulfonamidewith 4-(methylsulfonyl)-piperidine. Yield=92%; MS (ESI+), 567 (M+H)⁺.

EXAMPLE 844-Chloro-N-(2,5-dichlorophenyl)-N-[4-[(3-methylthio)-1-piperidinyl-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4-[(3-methylthio)-1-piperidinyl]-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith 3-(methylthio)piperidine. Yield=89%; MS (ESI+), 535 (M+H)⁺.

EXAMPLE 854-Chloro-(2,5-dichlorophenyl)-N-[4-[(3-methylsulfonyl)-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4-[(3-methylsulfonyl)-1-piperidinyl]-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith 3-(methylsulfonyl)-piperidine. Yield=93%; MS (ESI+), 567 (M+H)⁺.

EXAMPLE 864-Chloro-N-(2,5-dichlorophenyl)-N-[4-[(3-methylthio)-1-pyrrolidinyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4[(3-methylthio)-1-pyrrolidinyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith 3-(methylthio)-pyrrolidine. Yield=86%; MS (ESI+), 521 (M+H)⁺.

EXAMPLE 874-Chloro-N-(2,5-dichlorophenyl)-N-[4-[(3-methylsulfonyl)-1-pyrrolidinyl]-1(R)methylbutyl]benzenesulfonamide

4-chloro-N{2,5-dichlorophenyl)-N-[4-[(3-methylsulfonyl)-1-pyrrolidinyl]-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith 3-(methylsulfonyl)-pyrrolidine. Yield=88%; MS (ESI+), 553 (M+H)⁺.

EXAMPLE 884-Chloro-N-(2,5-dichlorophenyl)-N-(4-(2-(((R)methylsulfonyl)methyl)-1-pyrrolidinyl)-1(R)-methylbutyl)benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-(4-(2-(((R)-methylsulfonyl)methyl)-1-pyrrolidinyl)-1(R)-methylbutyl)benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith (R)-2-(methyl-sulfonyl])methyl)pyrrolidine. Yield=10%; yellow oil:IR (neat, CH₂Cl₂) 1349, 1301, 1166, 1130, 1094, 622, cm⁻¹; MS (ESI+),569 (M+H)⁺.

EXAMPLE 894-Chloro-N-(2,5-dichlorophenyl)-N-(4-(2-(((S)-methylsulfonyl)methyl)-1-pyrrolidinyl)-1(R)-methylbutyl)benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-(4-(2-(((S)-methylsulfonyl)methyl)—pyrrolidinyl)-1(R)-methylbutyl)benzenesulfonamidewas prepared analogous to4-chloro-N-2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting 4-chloro-N-[2,5-dichlorophenyl]-N-[(R)1-methyl-4-bromobutyl]benzenesulfonamide with(S)-(2-(methylsulfonyl)methyl)pyrrolidine. Yield=43%; yellow oil: IR(neat, CH₂Cl₂) 1467, 1350, 1302, 1167, 1094, 622, cm⁻¹; MS (ESI+), 569(M+H)⁺.

EXAMPLE 904-Chloro-N-2,5-dichlorophenyl)-N-[5-[3-[(methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylpentyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[5-[[3-(methylsulfonyl)methyl]-1-piperidinyl]]-1(R)-methylpentyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-5-bromopentyl]benzenesulfonamidewith 3-(methylsulfonylmethyl)piperidine. Yield=74%; MS (ESI+), 595(M+H)⁺.

EXAMPLE 914-Chloro-N-(2,5-dichlorophenyl)-N-[5-[(4-methylsulfonyl)-1-piperidinyl-1(R)-methylpentyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[5-[(4-methylsulfonyl)-1-piperidinyl]-1(R)-methylpentyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamide by reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-5-bromopentyl]benzenesulfonamidewith 4-methylsulfonyl)-piperidine. Yield=79%; MS (ESI+), 581 (M+H)⁺.

EXAMPLE 924-Chloro-N-(2,5-dichlorophenyl)-N-[5-[(3-methylsulfonyl)-1-piperidinyl]-1(R)-methylpentyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[5-[(3-methylthsulfonyl)-1-piperidinyl]-1(R)-methylpentyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-5-bromopentyl]benzenesulfonamidewith 3-(methylsulfonyl)-piperidine. Yield=82%; MS (ESI+), 581 (M+H)⁺.

EXAMPLE 934-Chloro-N-(2,5-dichlorophenyl)-N-[5-[(3-methylsulfonyl)-1-pyrrolidinyl]-1(R)-methylpentyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[5-[(3-methylthsulfonyl)-1-pyrrolidinyl]-1(R)-methylpentyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-5-bromopentyl]benzenesulfonamidewith 3-(methylsulfonyl)-pyrrolidine. Yield=72%; MS (ESI+), 567 (M+H)⁺.

EXAMPLE 944-Chloro-N-(2,5-dichlorophenyl)-N-(5-(4-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpentyl)benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[5-[[4-(methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylpentyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)1-piperidinyl)-1(R)methylpropyl)benzenesulfonamide by reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)1-methyl-5-bromopentyl]benzenesulfonamide with4-(methylsulfonylmethyl)piperidine. Yield=68%; yellow oil: IR (neat,CH₂Cl₂) 1467, 1301, 1166, 1136, 1093, 622 cm⁻¹; MS (ESI+), 595 (M+H)⁺.

EXAMPLE 954-Chloro-N-(2,5-dichlorophenyl)-N-(5-(2-(methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpentyl)benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[5-[[2-(methylsulfonyl)methyl]-1-piperidinyl-1(R)-methylpentyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-5-bromopentyl]benzenesulfonamidewith 2-(methyl-sulfonylmethyl)piperidine. Yield=73%; yellow oil: IR(neat, CH₂Cl₂) 1467, 1297, 1166, 1139, 1094, 623, cm⁻¹; MS (ESI+), 595(M+H)⁺.

EXAMPLE 964-Chloro-N-(2,5-dichlorophenyl)-N-(3-(2-carboxymethyl-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamide

4-chloro-N-2,5-dichlorophenyl)-N-3-(2-carboxymethyl-3-thiazolidinyl)-1(R)-methylpropyl)-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-3-bromopropyl]benzenesulfonamidewith 2-carboxymethyl-3-thiazolidine. Yield=6%; White powder: IR (KBr)1747, 1467, 1352, 1166, 1094, 622 cm⁻¹; MS (ESI+), 537 (M+H)⁺.

EXAMPLE 974-Chloro-N-(2,5-dichlorophenyl)-N-(3-(2-carboxymethyl-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-carboxymethyl-3-thiazolidinyl)-1(R)-methylpropyl)-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl-piperidinyl)-1(R)methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-3-bromopropyl]benzenesulfonamidewith 2-carboxymethyl-3-thiazolidine. Yield=7%; White powder: IR (KBr)1747, 1467, 1352, 1167, 1094, 622 cm⁻¹; MS (ESI+), 537 (M+H)⁺.

EXAMPLE 984-Chloro-N-(2,5-dichlorophenyl)-N-(4-(2-carboxymethyl-3-thiazolidinyl)-1(R)-methylbutyl)benzenesulfonamide

4-chloro-N′-(2,5-dichlorophenyl)-N-(4-(2-carboxymethyl-3-thiazolidinyl)-1(R)-methylbutyl)-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith 2-carboxymethy]-3-thiazolidine. Yield=25%; MS (ESI+), 551 (M+H)⁺.

EXAMPLE 994-Chloro-N-(2,5-dichlorophenyl)-N-(5-(2-carboxymethyl-3-thiazolidinyl)-1(R)-methylpentyl)benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-(5-(2-carboxymethyl-3-thiazolidinyl)-1(R)-methylpentyl)-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-5-bromopentyl]benzenesulfonamidewith 2-carboxymethyl-3-thiazolidine. Yield=39%; Colorless oil: IR (neat,CH₂Cl₂) 1748, 1467, 1352, 1167, 1095, 623 cm⁻¹; MS (ESI+), 565 (M+H)⁺.

EXAMPLE 1004-Chloro-N-(2,5-dichlorophenyl)-N-(3-(5-carboxymethyl-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamide-

4-chloro-N-(2,5-dichlorophenyl)-N-(3-(5-carboxymethyl-3-thiazolidinyl)-1(R)-methylpropyl)-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-3-bromopropyl]benzenesulfonamidewith 5-carboxymethyl-3-thiazolidine. Yield=31%; Colorless oil: IR (neat,CH₂Cl₂) 1742, 1467, 1352, 1167, 1094, 622 cm⁻¹; MS (ESI+), 539 (M+H)⁺.

EXAMPLE 1014-Chloro-N-(2,5-dichlorophenyl)-N-(3-(5-carboxymethyl-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-(3-(5-carboxymethyl-3-thiazolidinyl)-1(R)-methylpropyl)-benzenesulfonamidewas prepared analogous to4-chloro-N-2,5-dichlorophenyl)-N-(3-(2-((methylsulfonyl)methyl)-1-piperidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-3-bromopropyl]benzenesulfonamidewith 5-carboxymethyl-3-thiazolidine. Yield=21%; Colorless oil: IR (neat,CH₂Cl₂) 1738, 1467, 1351, 1167, 1095, 622 cm⁻¹; MS (ESI+), 539 (M+H)⁺.

EXAMPLE 1024-Chloro-N-(2,5-dichlorophenyl)-N-(3-(2-carboxy-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamide

To a stirring solution of4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-carboxymethyl-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamide(109 mg, 0.203 mmol) in methanol (20 mL) was added 50% aqueous KOH (1.0mL) and the mixture was stirred at room temperature for 18 hours. Thesolvent was removed and the crude mixture was dissolved in CH₂Cl₂ andwashed with 1N HCl. The CH₂Cl₂ layer was dried over Na₂SO₄ andevaporated to give crude product. Purification was performed over silicagel using 5-10% methanol in CH₂Cl₂ with 0.5% NH₄OH to afford4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-carboxy-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamideas a beige foam in 66% yield. IR (KBr) 1467, 1351, 1167, 1094, 753, 622cm⁻¹; MS (ESI+), 523 (M+H)⁺.

EXAMPLE 1034-Chloro-N-(2,5-dichlorophenyl-N-(4-(2-carboxy-3-thiazolidinyl)-1(R)-methylbutyl)benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-(4-(2-carboxy-3-thiazolidinyl)-1(R)-methylbutyl)benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-carboxy-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-(2,5-dichlorophenyl)-N-(4-(2-carboxymethyl-3-thiazolidinyl)-1(R)-methylbutyl)benzenesulfonamidewith 50% aqueous KOH. Yield=77%; White foam: IR (KBr) 1467, 1351, 1167,1093, 753, 622 cm⁻¹; MS (ESI+), 537 (M+H)⁺.

EXAMPLE, 1044-Chloro-N-(2,5-dichlorophenyl)-N-(5-(2-carboy-3-thiazolidinyl)-1(R)-methylpentyl)benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-(5-(2-carboxy-3-thiazolidinyl)-1(R)-methylpentyl)benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-carboxy-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-(2,5-dichlorophenyl)-N-(5-(2-carboxymethyl-3-thiazolidinyl)-1(R)-methylpentyl)benzenesulfonamidewith 50% aqueous KOH. Yield=67%; White foam: IR (neat, CH₂Cl₂) 1467,1350, 1167, 1093, 753, 622 cm⁻¹; MS (ESI+), 553 (M+H)⁺.

EXAMPLE 1054-Chloro-N-(2,5-dichlorophenyl)-N-(3-(5-carboxy-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-(3-(5-carboxy-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamidewas prepared analogous to4-chloro-N-2,5-dichlorophenyl)-N-(3-(2-carboxy-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-(2,5-dichlorophenyl)-N-(3-(5-carboxymethyl-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamidewith 50% aqueous KOH. Yield=70%; White foam: IR (KBr) 1467, 1350, 1167,1094, 753, 622 cm⁻¹; MS (ESI+), 525 (M+H)⁺.

EXAMPLE 1064-Chloro-N-5-(2,5-dichlorophenyl)-N-(4-(5-carboxy-3-thiazolidinyl)-1(R)-methylbutyl)benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-(4-(5-carboxy-3-thiazolidinyl)-1(R)-methylbutyl)benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-carboxy-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-(2,5-dichlorophenyl)-N-(4-(5-carboxymethyl-3-thiazolidinyl)-1(R)-methylbutyl)benzenesulfonamidewith 50% aqueous KOH. Yield=45%; White powder: IR (KBr) 1467, 1350,1167, 1094, 754, 622 cm⁻¹; MS (ESI+), 537 (M+H)⁺.

EXAMPLE 1074-Chloro-N-(2,5-dichlorophenyl)-N-(5-(5-carboxy-3-thiazolidinyl)-[(R)-methylpentyl)benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-(5-(5-carboxy-3-thiazolidinyl)-1(R)-methylpentyl)benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-(3-(2-carboxy-3-thiazolidinyl)-1(R)-methylpropyl)benzenesulfonamideby reacting4-chloro-N-(2,5-dichlorophenyl)-N-(5-(5-carboxymethyl-3-thiazolidinyl)-1(R)-methylpentyl)benzenesulfonamidewith 50% aqueous KOH, Yield=34%; White powder: IR (KBr) 1467, 1350,1167, 1094, 754, 623 cm⁻¹; MS (ESI+), 551 (M+H)⁺.

EXAMPLE 1084-Chloro-N-(2,5-dichlorophenyl)-N-[5-[N-(2,5-dichlorophenyl)-N-[(4-chlorophenyl)sulfonyl]amino]-1(R)-methylpentyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[5-[N-(2,5-dichlorophenyl)-N-[(4-chlorophenyl)-sulfonyl]amino]-1(R)-methylpentyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[4-(methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-(2,5-dichlorophenyl)-N-[4-bromo-1(R)-methylbutyl]benzenesulfonamidewith 4-chloro-N-(2,5-dichlorophenyl)benzenesulfonamide. Yield=20%; MS(ESI+), 771 (M+NH₃)⁺.

EXAMPLE 1094-Chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[(methylsulfonyl)amino]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[(methylsulfonyl)amino]-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to 4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[4(methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-bromo-1(R)-methylbutyl]benzenesulfonamidewith methanesulfonamide. Yield=89%; MS (ESI+), 483 (M+H)⁺.

EXAMPLE 1104-Chloro-N-(5-chloro-2-fluorophenyl)-N-4-[(methylsulfonyl)methylamino]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[(methylsulfonyl)methylamino]-1(R)methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[4-(methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-bromo-1(R)-methylbutyl]benzenesulfonamidewith N-methyl-methanesulfonamide. Yield=81%; MS (ESI+), 497 (M+H)⁺.

EXAMPLE 1114-Chloro-N-(5-chloro-2-fluorophenyl)-N-[4-(4-morpholinyl)-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-(morpholinyl)-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[4-(methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-bromo-1(R)-methylbutyl]benzenesulfonamidewith morpholine. Yield=87%; MS (ESI+), 475 (M+H)⁺.

EXAMPLE 1124-Chloro-N-(2,5-dichlorophenyl)-N-[4-nitro-1(R)-methylbutyl]benzenesulfonamide

To a solution of4-chloro-n-(2,5-dichlorophenyl)-n-[(r)-1-methyl-4-bromobutyl]benzenesulfonamide(0.216 g, 0.444 mmol) in ether (4 mL) was added AgNO₂ (0.410 g, 2.67mmol) at 22° C. The resulting mixture was allowed to stir at 22° C. for4 days and the mixture was filtered and concentrated under reducedpressure. Silica get chromatography (1:9 ethyl acetate:hexanes) of theconcentrate afforded 0.129 g of4-chloro-N-(2,5-dichlorophenyl)-N-[(R)-1-methyl-4-nitrobutyl]-benzenesulfonamideas a light brown oil in 64% yield. MS (ESI) 451.1 (M+h).

EXAMPLE 1134-Chloro-N-(2,5-difluorophenyl-N-[4-nitro-1(R)-methylbutyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamide(0.194 g, 0.427 mmol) in ether (4 mL) was added AgNO₂ (0.395 g, 2.56mmol) at 22° C. The resulting mixture was allowed to stir at 22° C. for4 days. The mixture was filtered and concentrated under reducedpressure. Silica gel chromatography (1:9 ethyl acetate:hexanes) of theconcentrate afforded 0.0913 g of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-4-nitrobutyl]]-benzenesulfonamideas a light brown oil in 50% yield. MS (ESI) 419.1 (M+H).

EXAMPLE 1144-Chloro-N-(5-chloro-2-fluorophenyl)-N-[4-nitro-1(R)-methylbutyl]benzenesulfon-amide

To a solution of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl-4-bromobutyl]-benzenesulfonamide(0.150 g, 0.320 mmol) in ether (4 mL) was added AgNO₂ (0.296 g, 1.92mmol) at 22° C. The resulting mixture was allowed to stir at 22° C. for4 days. The mixture was filtered and concentrated under reducedpressure. Silica gel chromatography (1:9 ethyl acetate:hexanes) of theconcentrate afforded 0.0746 g of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl-4-nitrobutyl]benzenesulfonamideas a light brown oil in 53% yield. MS (ESI) 435.1 (M+H).

EXAMPLE 1154-Chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl(acetylamino)butyl]benzenesulfonamide

To a solution of4-chloro-N-[2,5-dichlorophenyl]-N-[R]-1-methyl-4-aminobutyl]benzenesulfonamide(35.0 mg, 0.083 mmol) in CH₂Cl₂ (2 mL) was added acetic anhydride (0.024mL, 0.249 mmol) and pyridine (0.027 mL, 0.332 mmol) at 0° C. Theresulting mixture was allowed to stir at 22° C. overnight. To thereaction was added sat. sodium bicarbonate (20 mL). The product wasextracted with CH₂Cl₂ (2×20 mL), dried over Na₂SO₄, filtered, andconcentrated under reduced pressure. Silica gel chromatography (1:4ethyl acetate:hexanes) of the concentrate afforded 37.8 mg of4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-acetylamino)butyl]benzenesulfonamideas a colorless oil in 98% yield. MS (ESI) 463 (M+H).

EXAMPLE 1164-Chloro-N-(2,5-dichlorophenyl)-N-[4-[[[(S)hydroxy]phenylmethyl]carbonyl]amino]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[[(S)hydroxy]phenylmethyl]carbonyl]amino]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-(acetylamino)butyl]benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[R]-1-methyl-4-aminobutyl]benzenesulfonamidewith (S)—O-acetyl-mandelic chloride. Yield=64%; MS (ESI+), 555 (M+H)⁺.

EXAMPLE 1174-Chloro-N-(2,5-dichlorophenyl)-N-[4-[[[(R)hydroxy]phenylmethyl]carbonyl]amino]-1(R)methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[[(R)hydroxy]phenylmethyl]carbonyl]amino]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-(acetylamino)butyl]benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[R]-1-methyl-4-aminobutyl]benzenesulfonamidewith (O-acetyl-mandelic chloride. Yield=57%; MS (ESI+), 555 (M+H)⁺.

EXAMPLE 1184-Chloro-N-(2,5-dichlorophenyl)-N-[4-[[(1,1-dimethylethyl)carbonyl]amino]-1-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[(1,1-dimethylethyl)carbonyl]amino]-1-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-(acetylamino)butyl]benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[R]-1-methyl-4-aminobutyl]benzenesulfonamidewith pivaloyl chloride. Yield=86%; MS (ESI+), 505 (M+H)⁺.

EXAMPLE 1194-Chloro-N-(2,5-dichlorophenyl)-N-[4-[[(phenyl)carbonyl]amino]-1-methylbutyl]benzenesulfonamide

4-chloro-N-2,5-dichlorophenyl)-N-(4-[[(phenyl)carbonyl]amino]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-(acetylamino)butyl]benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[R]-1-methyl-4-aminobutyl]benzenesulfonamidewith benzoyl chloride. Yield=84%; MS (ESI+), 525 (M+H)⁺.

EXAMPLE 1204-Chloro-N-(2,5-dichlorophenyl)-N-[4-[[(methoxy)carbonyl]amino]-1-methylbutyl]benzenesulfonamide

4-chloro-N-2,5-dichlorophenyl)-N-[4-[[(methoxy)carbonyl]amino]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-(acetylamino)butyl]benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[R]-1-methyl-4-aminobutyl]benzenesulfonamidewith methyl chloroformate. Yield=96%; MS (ESI+), 479 (M+H)⁺.

EXAMPLE 1214-Chloro-N-(2,5-dichlorophenyl)-N-[4-[[(1,1-dimethylethoxy)carbonyl]amino]-1-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[(1,1-dimethylethoxy)phenylmethyl]carbonyl]amino]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-(acetylamino)butyl]benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[R]-1-methyl-4-aminobutyl]benzenesulfonamidewith di-tert-butyl dicarbonate. Yield=91%; MS (ESI+), 521 (M+H)⁺.

EXAMPLE 1224-Chloro-N-(2,5-dichlorophenyl)-N-[4-[[(phenoxy)carbonyl]amino]-1-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[(phenoxy)carbonyl]amino]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl(acetylamino)butyl]benzenesulfonamide by reacting4-chloro-N-[2,5-dichlorophenyl]-N-[R]-]-methyl-4-aminobutyl]benzenesulfonamidewith phenyl chloroformate. Yield=82%; MS (ESI+), 541 (M+H)⁺.

EXAMPLE 1234-Chloro-N-(2,5-dichlorophenyl)-N-[4-[[(benzoxy)carbonyl]amino]-1-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[(benzyloxy)carbonyl]amino]-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-(acetylamino)butyl]benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[R]-1-methyl-4-aminobutyl]benzenesulfonamidewith benzyl chloroformate. Yield=81%; MS (ESI+), 555 (M+H)⁺.

EXAMPLE 1244-Chloro-N-(2,5-dichlorophenyl)-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylbutyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-dichlorophenyl)-N-[(R)-1-methyl-4-aminobutyl]benzenesulfonamide(0.207 g, 0.463 mmol) in THF (3 mL) was added3,4-diisopropoxy-3-cyclobutene-1,2-dione (0.0963 g, 0.486 mmol)dissolved in THF (2 mL) at 22° C. under nitrogen atmosphere. Theresulting mixture was allowed to stir at 22° C. for 12 h. The mixturewas concentrated under reduced pressure. Silica gel chromatography (3:7ethyl acetate:hexanes) of the concentrate afforded 0.135 g of4-chloro-N-(2,5-dichlorophenyl])-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylbutyl]benzenesulfonamideas a white solid in 50% yield. MS (ESI) 559.2 (M+H).

EXAMPLE 1254-Chloro-N-(5-chloro-2-fluorophenyl)-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylbutyl]benzenesulfonamide

To a solution of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl-4-aminobutyl]-benzenesulfonamide(0.185 g, 0.455 mmol) in THF (4 mL) was added3,4-diisopropoxy-3-cyclobutene-1,2-dione (0.0948 g, 0.478 mmol)dissolved in THF (2 mL) at 22° C. under nitrogen atmosphere. Theresulting mixture was allowed to stir at 22° C. for 12 h. The mixturewas concentrated under reduced pressure. Silica gel chromatography (3:7ethyl acetate:hexanes) of the concentrate afforded 0.182 g of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylbutyl]benzenesulfonamideas a white solid in 74% yield. MS (ESI) 543.2 (M+H).

EXAMPLE 1264-Chloro-N-(2,5-difluorophenyl)-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylbutyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-4-aminobutyl]benzenesulfonamide(0.243 g, 0.635 mmol) in THF (7 mL) was added3,4-diisopropoxy-3-cyclobutene-1,2-dione (0.138 g, 0.698 mmol) dissolvedin THF (3 mL) at 22° C. under nitrogen atmosphere. The resulting mixturewas allowed to stir at 22° C. for 12 h. The mixture was concentratedunder reduced pressure. Silica gel chromatography (3:7 ethylacetate:hexanes) of the concentrate afforded 0.135 g of4-chloro-N-(2,5-difluorophenyl)-N-4-(2-isopropoxy-3,4-dioxo-1cyclobutenyl)amine-1(R)-methylbutyl]benzenesulfonamide as a white solidin 47% yield. MS (ESI) 527.2 (M+H).

EXAMPLE 1274-Chloro-N-(2,5-dichlorophenyl)-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylpropyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-dichlorophenyl)-N-[(R)-1-methyl-3-aminopropyl]benzenesulfonamide(0.328 g, 0.805 mmol) in THF (6 mL) was added3,4-diisopropoxy-3-cyclobutene-1,2-dione (0.176 g, 0.885 mmol) dissolvedin THF (2 mL) at 22° C. under nitrogen atmosphere. The resulting mixturewas allowed to stir at 22° C. for 12 h. The mixture was concentratedunder reduced pressure. Silica gel chromatography (3:7 ethylacetate:hexanes) of the concentrate afforded 0.185 g of4-chloro-N-2,5-dichlorophenyl)-N-[3-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylpropyl]benzene-sulfonamideas a white solid in 80% yield. MS (ESI) 545 (M+H).

EXAMPLE 1284-Chloro-N-(5-chloro-2-fluorophenyl)-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylpropyl]benzenesulfonamide

To a solution of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(R)-1-methyl-3-aminopropyl]-benzenesulfonamide(0.389 g, 0.995 mmol) in THF (7 mL) was added3,4-diisopropoxy-3-cyclobutene-1,2-dione (0.217 g, 1.09 mmol) dissolvedin THF (3 mL) at 22° C. under nitrogen atmosphere. The resulting mixturewas allowed to stir at 22° C. for 12 h. The mixture was concentratedunder reduced pressure. Silica gel chromatography (3:7 ethylacetate:hexanes) of the concentrate afforded 0.243 g of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[3-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylpropyl]benzenesulfonamideas a white solid in 46% yield. MS (ESI) 529.1 (M+H).

EXAMPLE 1294-Chloro-N-2,5-difluorophenyl)-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylpropyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-3-aminopropyl]benzenesulfonamide(0.401 g, 1.07 mmol) in THF (6 mL) was added3,4-diisopropoxy-3-cyclobutene-1,2-dione (0.233 g, 1.18 mmol) dissolvedin THF (4 mL) at 22° C. under nitrogen atmosphere. The resulting mixturewas allowed to stir at 22° C. for 12 h. The mixture was concentratedunder reduced pressure. Silica gel chromatography (3:7 ethylacetate:hexanes) of the concentrate afforded 0.392 g of4-chloro-N-2,5-difluorophenyl)-N-[3-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylpropyl]-benzenesulfonamideas a white solid in 71% yield. MS (ESI) 513.1 (M+H).

EXAMPLE 1304-Chloro-N-(2,5-dichlorophenyl)-N-[3-[2-[4-chloro-N-(2,5-dichlorophenyl)-N-[(3-amino)-1(R)-methylpropyl]benzenesulfonamide]-3,4-dioxo-1-cyclobutenyl]amine-1(R)-methylpropyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-dichlorophenyl)-N-[(R)-1-methyl-4-aminobutyl]benzenesulfonamide(0.125 g, 0.367 mmol) in methanol (3.0 mL) was added4-chloro-N-(2,5-dichlorophenyl)-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylpropyl]benzenesulfonamide(0.167 g, 0.306 mmol) at 22° C. The resulting mixture was heated toreflux for 12 hours. The desired compound precipitated while the mixturecooled to 22° C. The mixture was filtered, washed with ethyl acetate (4mL×2), and dried under reduced pressure to afford 0.140 g of4-chloro-N-(2,5-dichlorophenyl)-N-[3-[2-[4-chloro-N-(2,5-dichlorophenyl)-N-[(3-amino)-1(R)-methylpropyl]benzenesulfonamide]-3,4-dioxo-1-cyclobutenyl]amine-1(R)-methylpropyl]benzenesulfonamideas a white solid in 52% yield. MS (ESI) 893.1 (M+H).

EXAMPLE 1314-Chloro-N-(5-chloro-2-fluorophenyl)-N-[3-[2-[4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(3-amino)-1(R)-methylpropyl]benzenesulfonamide]-3,4-dioxo-1-cyclobutenyl]amine-1(R)-methylpropyl]benzenesulfonamide

To a solution of4-chloro-N-(5-fluoro-2-chlorophenyl)-N-[(R)-1-methyl-4-aminobutyl]-benzenesulfonamide(0.189 g, 0.483 mmol) in methanol (4.0 mL) was added4-chloro-N-(5-fluoro-2-chlorophenyl)-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)-amine-1(R)-methylpropyl]benzenesulfonamide(0.214 g, 0.403 mmol) at 22° C. The resulting mixture was heated toreflux for 12 hours. The desired compound precipitated while the mixturecooled to 22° C. The mixture was filtered, washed with ethyl acetate (4mL×2), and dried under reduced pressure to afford 0.174 g of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[3-[2-[4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(3-amino)-1(R)-methylpropyl]benzenesulfonamide]-3,4-dioxo-1-cyclobutenyl]amine-1(R)-methylpropyl]benzenesulfonamideas a white solid in 50% yield. MS (ESI) 861.1 (M+H).

EXAMPLE 1324-Chloro-N-(2,5-difluorophenyl)-N-[3-[2-[4-chloro-N-(2,5-difluorophenyl)-N-[(3-amino)-1(R)-methylpropyl]benzenesulfonamide]-3,4-dioxo-1-cyclobutenyl]amine-1(R)-methylpropyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-4-aminobutyl]-benzenesulfonamide(0.140 g, 0.374 mmol) in methanol (3.0 mL) was added4-chloro-N-(2,5-difluorophenyl)-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylpropyl]benzenesulfonamide(0.159 g, 0.311 mmol) at 22° C. The resulting mixture was heated atreflux to 12 hours. The desired compound precipitated while the mixturecooled to 22° C. The mixture was filtered, washed with ethyl acetate (3mL×2), and dried under reduced pressure to afford 0.124 g of4-chloro-N-(2,5-difluorophenyl)-N-[3-[2-[4-chloro-N-(2,5-difluorophenyl)-N-[(3-amino)-1(R)-methylpropyl]benzenesulfonamide]-3,4-dioxo-1-cyclobutenyl]amine-1(R)-methylpropyl]benzenesulfonamideas a white solid in 48% yield. MS (ESI) 5′ 827.2 (M+H).

EXAMPLE 1334-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamide

To a solution of4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[(R)-1-methyl-4-bromobutyl-benzenesulfonamide(0.650 g, 1.24 mmol) in tetrahydrofuran (2 mL) was added sodiumthioethoxide (0.115 g, 1.36 mmol) under nitrogen at 0° C. The mixturewas stirred overnight at 22° C. The mixture was quenched with 2M NaOH (3mL), extracted with ethyl ether (2×20 mL), dried over Na₂SO₄, andfiltered. The organic solvent was concentrated under reduced pressure.Silica gel chromatography (1:9 ethyl acetate:hexanes) afforded 0.500 gof4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamideas a yellow oil in 87% yield. MS (ESI+), 462 (M+H)+.

EXAMPLE 1344-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-methylthio)butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(methylthio)]-1R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[(R)-1-methyl-4-bromobutyl-benzenesulfonamidewith sodium thiomethoxide. Yield=77%; MS (ESI+), 448 (M+H)+.

EXAMPLE 1354-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-(methyl-(4-[(1-methylethyl)thio]butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[(1-methylethyl)thio]-1-(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[(R)-1-methyl-4-bromobutyl-benzenesulfonamidewith sodium thio-iso-propoxide. Yield=84%; MS (ESI+), 476 (M+H)+.

EXAMPLE 1364-Chloro-N-[5-chloro-2-hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-[(1,1-dimethylethyl)thio]butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-[(1,1-dimethylethyl)thio]butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[(R)-1-methyl-4-bromobutyl-benzenesulfonamidewith sodium thio-tert-butoxide. Yield=84%; MS (ESI+), 490 (M+H)+.

EXAMPLE 1374-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-phenylthio)butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(phenylthio)]-1-(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(ethylthio)]-1-(R)methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[(R)-1-methyl-4-bromobutyl-benzenesulfonamidewith sodium thiophenoxide. Yield=79/o; MS (ESI+), 510 (M+H)+.

EXAMPLE 1384-Ethylthio-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-ethylthio)butyl]benzenesulfonamide

To a solution of4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl}-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamide(1.00 g, 1.91 mmol) in DMF (4 mL) was added sodium thioethoxide (0.535g, 7.63 mmol) under nitrogen at 0° C. The mixture was stirred overnightat 22° C. The mixture was quenched with H₂O (3 mL), extracted with ethylether (2×20 mL), dried over Na₂SO₄, and filtered. The organic solventwas concentrated under reduced pressure. Silica gel chromatography (1:9ethyl acetate:hexanes) afforded 0.123 g of4-ethylthio-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamideas a yellow oil in 14% yield. MS (ESI+), 488 (M+H)+.

EXAMPLE 1394-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[ethyl)sulfonyl]-1-(R)-methylbutyl]benzenesulfonamide

4-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(ethyl)sulfinyll]-1-(R)-methylbutyl]benzenesulfonamide

To a solution of 4-chloro-N-[5-chloro-2-(hydroxymethylphenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamide (0.088 g,0.190 mmol) in CH₂Cl₂ (2 mL) was added 80% 3-chloroperoxybezoic acid(0.062 g, 0.285 mmol) at 0° C. Stirring was continued for 2 h at 22° C.The mixture was quenched with H₂O (10 mL), extracted with CH₂Cl₂ (2×20mL), dried over Na₂SO₄, and filtered. Solvent was concentrated underreduced pressure to afford a yellow oil. Silica gel chromatography (2%methanol:CH₂Cl₂, 5% methanol:CH₂Cl₂) gave 48.7 mg of4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[(ethyl)sulfonyl]-1-(R)-methylbutyl]benzenesulfonamidein 52% yield and 39.8 mg of 4-chloroN-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[ethyl)sulfinyl]-1-(R)-methylbutyl]benzenesulfonamidein 44% yield; MS (ESI) 494 (M+1); MS (ESI) 478 (M+1).

EXAMPLE 1404-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-methylsulfinyl)butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-methylsulfinyl)butyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(ethyl)sulfinyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-methylthio)]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=61%; MS (ESI+), 464 (M+H)+.

EXAMPLE 1414-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-methylsulfonyl)butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl-N-[1(R)-methyl-(4-methylsulfonyl)butyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[ethyl)sulfonyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[-(methylthio)]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=71%; MS (ESI+), 480 (M+H)+.

EXAMPLE 1424-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-[(1-methylethyl)sulfinyl]butyl]benzenesulfonamide

4chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[(1-methylethyl)sulfinyl]-1-(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(ethyl)sulfinyl]-1-(R)methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[(1-methylethyl)thio]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=43%; MS (ESI+), 492 (M+H)+.

EXAMPLE 1434-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4[(1-methylethyl)sulfonyl]butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[(1-methylethyl)sulfinyl]-1-(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(ethyl)sulfonyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[S-chloro-2-(hydroxymethyl)phenyl]-N-[(1-methylethyl)thio]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=46%; MS (ESI+), 508 (M+H)+.

EXAMPLE 1444-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-[(1,1-dimethylethyl)sulfinyl]butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-[(1,1-dimethylethyl)sulfinyl]butyl]benzenesulfonamide wasprepared analogous to4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-(4-(ethyl)sulfinyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)methyl-(4-[(1,1-dimethylethyl)thio]butyl]-benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=50%; MS (ESI+), 506 (M+H)+.

EXAMPLE 1454-Chloro-N-(5-chloro-2-hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-[(1,1-dimethylethyl)sulfonyl]butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-4-[(1,1-dimethylethyl)sulfonyl]butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[S-chloro-2-(hydroxymethyl)phenyl]-N-[4-(ethyl)sulfonyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-[(1,1-dimethylethyl)thio]butyl]-benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=41%; MS (ESI) 522 (M+1).

EXAMPLE 1464-Ethylsulfonyl-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-ethylsulfonyl)butyl]benzenesulfonamide

To a solution of4-ethylthio-N-[5-chloro-2-hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-ethylthio)butyl]benzenesulfonamide(0.123 g, 0.267 mmol) in CH₂Cl₂ (3 mL) was added 80%3-chloroperoxybezoic acid (0.231 g, 1.07 mmol) at 0° C. Stirring wascontinued for 2 h at 22° C. The mixture was quenched with H₂O (10 mL),extracted with CH₂Cl₂ (2×20 mL), dried over Na₂SO₄, and filtered.Solvent was concentrated under reduced pressure to afford a yellow oil.Silica gel chromatography (2% methanol:CH₂Cl₂, 5% methanol:CH₂Cl₂) gave99.3 mg of4-ethylsulfonyl-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[1(R)-methyl-(4-ethylsulfonyl)butyl]benzenesulfonamidein 71% yield. MS (ESI+), 569 (M+NH3)−.

EXAMPLE 1474-Chloro-N-[2,5-dichlorophenyl]-N-[4-(ethylthio)]-1(R)-methylbutyl]benzenesulfonamide

To a solution of NaH (0.025 g, 1.03 mmol) in tetrahydrofuran (2 mL) wasadded ethanethiol (0.096 g, 1.54 mmol), followed by4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamide(0.500 g 1.03 mmol) under nitrogen at 0° C. The reaction was stirredovernight at 22° C. The mixture was quenched with H₂° (3 mL), extractedwith ethyl ether (2×10 mL), dried over Na₂SO₄, and filtered. The organicsolvent was concentrated under reduced pressure. Silica gelchromatography (1:9, ethyl acetate:hexanes) afforded 0.460 g of4-chloro-N-[2,5-dichlorophenyl}-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamideas a yellow oil in 59% yield. LC/MS 466.

EXAMPLE 1484-Chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-methylthio)butyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-methylthio)butyl]benzenesulfonamideprepared analogous to4-chloro-1N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-ethylthio)butyl]-benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-1(R)-1-methyl-4-bromobutyl]-benzenesulfonamidewith sodium thiomethoxide. Yield=100%; MS (ESI+), 452 (M+H)+.

EXAMPLE 1494-Chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(1-methylethyl)thio[butyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)methyl-(4-[(1-methylethyl)thio]butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4ethylthio)butyl]benzenesulfonamide by reacting 1chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith sodium thio-iso-propoxide. Yield=100%; MS (ESI+), 478 (M−H)+.

EXAMPLE 1504-Chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(2-methylpropyl)thio)sulfonyl]butyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)methyl-(4[(2-methylpropyl)thio)sulfonyl]butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl(4-ethylthio)butyl]benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith sodium thio-iso-butoxide. Yield=100%; MS (ESI+), 494 (M+H)⁺.

EXAMPLE 1514-Chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)-methyl-(4-methylthio)butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-fluorophenyl]-N-[4-(methylthio)]-1-(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-fluorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith sodium thiomethoxide. Yield=98%; MS (ESI+), 436 (M+H)⁺.

EXAMPLE 1524-Chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)-methyl-(4-ethylthio)butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-fluorophenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-fluorophenyl]-N-[(R)-1-methyl-4-bromobutyl)benzenesulfonamidewith sodium thioethoxide. Yield=92%; MS (ESI+), 450 (M+H)+.

EXAMPLE 1534-Chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-methylthio)butyl]benzenesulfonamide

4-chloro-N-[2,5-difluorophenyl]-N-[1(R)methyl-(4-methylthio)butyl]benzenesulfonamide was prepared analogousto4-chloro-N-[2,5-dichlorophenyl]-N-[4-[ethyl)thio]-1-(R)methylbutyl]-benzenesulfonamideby reacting4-chloro-N-[2,5-difluorophenyl]-N-[(R)-1-methyl-4-bromobutyl]-benzenesulfonamidewith sodium thiomethoxide. Yield=97%; MS (ESI+), 420 (M+H)+.

EXAMPLE 1544-Chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl(4-ethylthio)butyl]benzenesulfonamide

4-chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-ethylthio)butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-(ethyl)thio]-1-(R)-methylbutyl]-benzenesulfonamideby reacting4-chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-bromo)butyl]-benzenesulfonamidewith sodium thioethoxide. Yield=96%; MS (ESI+), 434 (M+H)+.

EXAMPLE 1554-Chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-[(1-methylethyl)thio]butyl]benzenesulfonamide

4-chloro-N-[2,5-difluorophenyl]-N-[1(R)methyl-(4[(1-methylethyl)thio]butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-(ethyl)thio]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[2,5-difluorophenyl]-N-[(R)-1-methyl-4-bromobutyl]benzenesulfonamidewith sodium thio-iso-propoxide. Yield=89%; MS (ESI+), 448 (M+H)+.

EXAMPLE 1564-Chloro-N-[2,5-dichlorophenyl]-N-[4-(ethyl)sulfinyl]-1-(R)-methylbutyl]benzenesulfonamide

4-Chloro-N-[2,5-dichlorophenyl]-N-[4-(ethyl)sulfonyl]-1-(R)methylbutyl]benzenesulfonamide

To a solution of4-chloro-N-[2,5-dichlorophenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamide(0.460 g, 0.600 mmol) in CH₂Cl₂ (6 mL) was added 80%3-chloroperoxybezoic acid (0.166 g, 0.957 mmol) at 0° C. Stirring wascontinued for 2 h at 22° C. The mixture was quenched with 1120 (10 mL)extracted with CH₂Cl₂ (2×10 mL), dried over Na₂SO₄, and filtered.Solvent was concentrated under reduced pressure to afford a yellow oil.Silica gel chromatography (2% methanol:CH₂Cl₂, 5% methanol:CH₂Cl₂) gave0.170 g of4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(ethyl)sulfonyl]-(R)-methylbutyl]benzenesulfonamidein 56% yield and 0.130 g of4-chloro-N-[2,5-dichlorophenyl]-N-[4-[ethyl)sulfoxyl]-1-(R)-methylbutyl]benzenesulfonamide in 44% yield. MS (ESI) 498 (M+1); MS (ESI) 482 (M+1).

EXAMPLE 1574-Chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-methylsulfinyl)butyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)methyl(4-methylsulfinyl)butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-(ethyl)sulfinyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[4-(methylthio)]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=47%; MS (ESI+), 466 (M—H)+.

EXAMPLE 1584-Chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-methylsulfonyl)butyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[I(R)-methyl-(4-methylsulfonyl)butyl]benzenesulfonamide was preparedanalogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4[ethyl)sulfonyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl)-N-[4-(methylthio)]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=42%; MS (ESI+), 482 (M−H)+.

EXAMPLE 1594-Chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(1-methylethyl)sulfinyl]butyl]benzenesulfonamide

4-chloro-N′-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(1-methylethyl)sulfinyl]butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[ethyl)sulfinyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting 4-chloro-N-[2,5-dichlorophenyl]-N-[I(R)-methyl-(4-[(1-methylethyl)thio]butyl]benzenesulfonamide with3-chloroperoxybezoic acid. Yield=54%; MS (ESI+), 496 (M+H)+.

EXAMPLE 1604-Chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(1-methylethyl)sulfonyl]butyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(1-methylethyl)sulfonyl]butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[ethyl)sulfonyl]-1-(Remethylbutyl]benzenesulfonamide by reacting4-chloro-N-[2,5-dichlorophenyl-N′-[1(R)-methyl-(4-[(]-methylethyl)thio]butyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=38%; MS (ESI+), 512 (M+H)+.

EXAMPLE 1614-Chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(2-methylpropyl)sulfinyl]butyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(2-methylpropyl)sulfinyl]butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[ethyl)sulfinyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(2-methylpropyl)thio]butyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=29%; MS (ESI+), 508 (M−H)+.

EXAMPLE 1624-Chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(2-methylpropyl)sulfonyl]butyl]benzenesulfonamide

This compound was prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4(ethyl)sulfonyl]-1-(R)-methylbutyl]benzenesulfonamide by reacting4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(2-methylpropyl]thio]butyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=35%; MS (ESI+), 526 (M+H)+.

EXAMPLE 1634-Chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)-methyl-(4-methylsulfinyl)butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)-methyl-(4-methylsulfinyl)butyl]benzenesulfonamide was preparedanalogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-(ethyl)sulfinyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-fluorophenyl]-N-[4-(methylthio)]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=61%; MS (ESI+), 452 (M+H)+.

EXAMPLE 1644-Chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)-methyl-(4-methylsulfonyl)butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)-methyl-(4-methylsulfonyl)butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-2,5-dichlorophenyl]-N-[4-(ethyl)sulfonyl]-1-(R)-methylbutyl]benzenesulfonamide by reacting4-chloro-N-[5-chloro-2-fluorophenyl]-N-[4-(methylthio)]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=37%; MS (ESI+), 466 (M−H)+.

EXAMPLE 1654-Chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)-methyl-(4-ethylsulfinyl)butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)-methyl-(4-ethylsulfinyl)butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-ethyl)sulfinyl]1-]-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-flurophenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=48%; MS (ESI+), 466 (M+H)+.

EXAMPLE 1664-Chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)-methyl-(4-ethylsulfonyl)butyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)methyl-(4-ethylsulfonyl)butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-(ethyl)sulfonyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[5-chloro-2-fluorophenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=44%; MS (ESI+), 482 (M+H)+.

EXAMPLE 1674-Chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-methylsulfinyl)butyl]benzenesulfonamide

4-chloro-N-[2,5-difluorophenyl]-N-[1(R)methyl-(4-methylsulfinyl)butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-(ethyl)sulfinyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[2,5-diflurophenyl]-N-[4-(methylthio)]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=35%; MS (ESI+), 436 (M+H)+.

EXAMPLE 1684-Chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-methylsulfonyl)butyl]benzenesulfonamide

4-chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-methylsulfonyl)butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-(ethyl)sulfonyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[2,5-diflurophenyl]-N-[4-(methylthio)]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=30%; MS (ESI+), 452 (M+H)+.

EXAMPLE 1694-Chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-ethylsulfinyl)butyl]benzenesulfonamide

4-chloro-N-[2,5-difluorophenyl]-N-[1(R)methyl-(4-ethylsulfinyl)butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-(ethyl)sulfinyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[2,5-diflurophenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=40%; MS (ESI+), 450 (M+H)+.

EXAMPLE 1704-Chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-ethylsulfonyl)butyl]benzenesulfonamide

4-chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-ethylsulfonyl)butyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-(ethyl)sulfonyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-12,5-diflurophenyl]-N-[4-(ethylthio)]-1-(R)-methylbutyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=57%; MS (ESI+), 466 (M+H)+.

EXAMPLE 1714-Chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-[(1-methylethyl)sulfinyl]butyl]benzenesulfonamide

4-chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-[(1-methylethyl)sulfinyl]butyl]benzenesulfonamide wasprepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[1(ethyl)sulfinyl]-1-(R)-methylbutyl]benzenesulfonamideby reacting4-chloro-N-[2,5-diflurophenyl]-N-[1(R)-methyl-(4[(1-methylethyl)thio]butyl]benzenesulfonamidewith 3-chloroperoxybezoic acid. Yield=32%; MS (ESI+), 464 (M+H)+.

EXAMPLE 1724-Chloro-N-[2,5-dichlorophenyl]-N-[1(R)methyl-(3-ethylthio)propyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-dichlorophenyl)-N-[1(R)-methyl-(3-iodo)propyl]benzenesulfonamide(0.500 g, 0.960 mmol) in THF (2 mL) was added sodium thioethoxide (0.080g, 0.960 mmol) at 22° C. The reaction was allowed to stir for 12 h at22° C. The solvent was removed, the residue was taken into CH₂Cl₂ (50mL) and washed with water (50 mL). The organic solution was dried overNa₂SO₄, filtered and concentrated to afford (0.330 g) of4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(3-ethylthio)propyl]benzenesulfonamideas a colorless oil in 77% yield. MS (ESI+), (M+H)+.

EXAMPLE 1734-Chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(3-ethylsulfonyl)propyl]benzenesulfonamide

To a solution of4-chloro-N-[2,5-dichlorophenyl]-N-[(R)-1-methyl-(3-ethylthio)propyl]benzenesulfonamide(0.330 g, 0.730 mmol) was added 3-chloroperoxybenzoic acid, (0.250 g,0.960 mmol) in THF (50 mL) at 22° C. After 2 h the mixture was washedwith water (50 mL) and extracted with ether (50 mL). The organicsolution was dried over Na₂SO₄, filtered and concentrated under reducedpressure. Silica gel chromatography (5% CH₂Cl₂/methanol) of theconcentrate gave 0.198 g of4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(3-ethylsulfonyl)propyl}benzenesulfonamidein 56% yield. MS ESI (483).

EXAMPLE 1744-Chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(5-ethylthio)pentyl]benzenesulfonamide

To a solution of 4-chloro-N-(2,5-dichlorophenyl)-N-[1(R)-methyl-(5-iodo)pentyl]benzenesulfonamide (0.500 g, 0.938 mmol) inTHF (8 mL) was added sodium thioethoxide (0.078 g, 9.38 mmol) at 22° C.After 12 h the solvent was removed, the residue was taken into CH₂Cl₂(50 mL) and washed with water. The organic solution was dried overNa₂SO₄, filtered and concentrated to afford (0.300 g) of4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl(5-ethylthio)pentyl]benzenesulfonamideas a colorless oil in 67% yield.

EXAMPLE 1754-Chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(5-ethylsulfonyl)pentyl]benzenesulfonamide

To a solution of4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(5-ethylthio)pentyl]benzenesulfonamide(0.300 g, 0.650 mmol) was added 3-chloroperoxybenzoic acid, (0.170 g,0.970 mmol) in CH₂Cl₂ (1.5 mL). Stirring was continued for 2 h at 22° C.The product was washed with water (50 mL) and extracted with CH₂Cl₂ (50mL). The organic solution was dried over Na₂SO₄, filtered andconcentrated under reduced pressure. Silica gel chromatography (5%CH₂Cl₂/methanol) of the concentrate gave 0.062 g of4-chloro-N-[2,5-dichlorophenyl]-N-[1 (R)-methyl-(5-ethylsulfonyl)pentyl]benzenesulfonamide in 19% yield. MS ESI (511).

EXAMPLE 176Methyl(5R)-5-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thiohexanoate

To a solution of4-chloro-N-(2,5-dichlorophenyl)-N-[(R)-1-methyl(2-iodoethyl)]benzenesulfonamide(0.840 g, 1.66 mmol) and methyl thioglycolate (1.05 g, 9.90 mmol) indiethyl ether was added triethylamine (1.33 g, 13.2 mmol) at 22° C. Thismixture was heated to reflux for 12 h. The product was washed withaqueous NaHCO₃ extracted with diethyl ether, dried over Na₂SO₄ andfiltered. Concentration in vacuo, followed by silica gel chromatography(15% ethyl acetate/hexanes) of the concentrate produced the titlecompound (800 mg, 98% yield).

EXAMPLE 177Methyl(5R)-5-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thiohexanoicAcid

To a solution of methyl(5R)-5-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thiohexanoate(0.050 g, 1.00 mmol) in methanol (1 mL) was added 1 mL of 0.5M sodiumhydroxide at 22° C. The mixture was stirred for 1 h. The methanol wasevaporated. The residue was diluted with ether and washed with water.The collected aqueous layer was acidified with 1N hydrochloride, andextracted with ether (2×50 mL). The organic layer was dried over Na₂SO₄,filtered and concentrated under reduced pressure to afford methyl(5R)-5-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thiohexanoate(33.3 mg, 70% yield). MS ESI (467).

EXAMPLE 178Methyl(5R)-5-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thiohexanoate,3Oxide

To a solution ofmethyl(5R)-5-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thiohexanoate(0.790 g, 1.70 mmol) in CH₂Cl₂ (2 mL) was added 3-chloroperoxybenzoicacid (0.350 g, 2.00 mmol) at 22° C. The mixture was allowed to stirredfor 2 h. The mixture was diluted with CH₂Cl₂, washed with water, driedover Na₂SO₄ and filtered. Silica gel chromatography (10%CH₂Cl₂/methanol) affordedmethyl(5R)-5-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thiohexanoate,3oxide (0.380 g, 46% yield). MS ESI (497).

EXAMPLE 179Methyl(6R)-6-[(2,5,dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thioheptanoate

To a solution of4-chloro-N-(2,5-dichlorophenyl)-N-[1(R)methyl-(3-iodo)-propyl]benzenesulfonamide(0.850 g, 1.64 mmol) and methyl thioglycolate (0.174 g, 1.60 mmol) indiethyl ether was added triethylamine (1.94 g, 1.92 mmol) at 22° C. Thismixture was heated to reflux for 12 h. The product was washed withaqueous NaHCO₃, extracted with diethyl ether, dried over Na₂SO₄ andfiltered. Concentration under reduced pressure, followed by silica gelchromatography (15% ethyl acetate/hexane) of the concentrate producedmethyl(6R)-6-[(2,5,dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thioheptanoate(0.650 g, 80% yield). MS ESI (495).

EXAMPLE 180(6R)-6-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thioheptanoicAcid

To a solution ofmethyl(6R)-6-[(2,5,dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino)-3-thioheptanoate(0.100 g, 0.200 mmol) 2 mL of methanol was added 1M sodium hydroxide (1mL) at 22° C. The mixture was stirred for 1 h and the methanol wasevaporated. The residue was diluted with ether and washed with water.The collected aqueous layer was acidified with 1N hydrochloride, andextracted with ether (3×25 mL). The organic layer was dried over Na₂SO₄,filtered and concentrated under reduced pressure to afford(6R)-6-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thioheptanoicacid (0.090 g, 90%/o yield). MS ESI (481).

EXAMPLE 181Methyl(6R)-6[(2,5,dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thioheptanoate,3-Oxide

Methyl(6R)-6-[(2,5,dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thioheptanoate,3,3 Dioxide

To a solution ofmethyl(6R)-6-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thioheptanoate(0.650 g, 1.30 mmol) in CH₂Cl, (5 mL) was added 3-chloro-peroxybenzoicacid (0.452 g, 2.60 mmol) at 22° C. The mixture was allowed to stir for2 h. The solution was washed with water, A” extracted with CH₂Cl₂, driedover Na₂SO₄ and filtered. Silica gel chromatography (10%CH₂Cl₂/methanol) of the concentrate afforded (0.380 g) ofmethyl(6R)-6[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino-3-thioheptanoate,3-oxide in 46% yield and (0.340 g) of methyl(6R)-6-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thio heptanoate, 3,3 dioxide in 50%yield. MS ESI (511). MS ESI (527).

EXAMPLE 182(6R)-6-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino-3-thioheptanoicAcid, 3-Oxide

To a solution ofmethyl(6R)-6-[(2,5,dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thioheptanoate,3-oxide (0.150 g, 0.290 mmol) in 4 mL of methanol was added 1M sodiumhydroxide (2 mL) at 22° C. The mixture was stirred for 1 h and themethanol was evaporated. The residue was diluted with ether and washedwith water. The collected aqueous layer was acidified with 1Nhydrochloride, and extracted with ether (3×50 mL). The organic layer wasdried over Na₂SO₄, filtered and concentrated under reduced pressure toafford(6R)-6-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thioheptanoicacid, 3-oxide (0.130 g, 85% yield). MS ESI (497).

EXAMPLE 183(6R)-6-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thioheptanoicAcid, 3,3 Dioxide

To a solution ofmethyl(6R)-6-[(2,5,dichlorophenyl)[(4-chlorophenyl)sulfonyl]amino]-3-thioheptanoate,3,3 dioxide (0.150 g, 2.90 mmol) in 4 mL of methanol was added 1M sodiumhydroxide (2 mL) at 22° C. The mixture was stirred for 1 h and themethanol was evaporated. The residue was diluted with ether and washedwith water. The collected aqueous layer was acidified with 1Nhydrochloride, and extracted with ether (3×50 mL). The organic layer wasdried over Na₂SO₄, filtered and concentrated under reduced pressure toafford(6R)-6-[(2,5-dichlorophenyl)[(4-chlorophenyl)sulfonyl)amino]-3-thioheptanoicacid, 3,3 dioxide (0.140 g, 90% yield). MS ESI (513).

EXAMPLE 1844-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

To a solution of(4R)-4-[5-chloro-2-(acetoxymethyl)phenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride (150 mg, 0.276 mmol) in CH₂Cl₂ (2 ml) was added a 2M THFsolution of methylamine (1.38 mL, 2.76 mmol). The mixture was stirred at22° C. overnight. 1N HCl (1 mL) was added to the mixture, followed byextraction with CH₂Cl₂. The organic layer was dried over Na₂SO₄,filtered, and concentrated under reduced pressure to afford a colorlessoil. This oil was purified by prep HPLC to afford4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamidein 64% yield. MS (ESI) 495 (M+1).

EXAMPLE 1854-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(aminosulfonyl)-1(R)-methylbutyl]-benzenesulfonamide

4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(aminosulfonyl)-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[5-chloro-2-(acetoxymethyl)phenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with ammonia.

Yield=60%; MS (ESI+), 481 (M+H)⁺.

EXAMPLE 1864-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[(dimethylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-(dimethylaminoaminosulfonyl)-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[5-chloro-2-(acetoxymethyl)phenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with dimethylamine. Yield=73%; MS (ESI+), 509 (M+H)⁺.

EXAMPLE 1874-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4[N-cyclopropylmethyl)-N-[3-(1H-imidazol-1-yl)propyl]aminosulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[N-(cyclopropylmethyl)-N-[3-(1H-imidazol-1-yl)propyl]aminosulfonyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[(methylamino)sulfonyl]-1(R)methylbutyl]benzenesulfonamideby reacting(4R)-4-[5-chloro-2-(acetoxymethyl)phenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with N-(cyclopropylmethyl)-N-[3-(1H-imidazol-1-yl)propyl]amine.

Yield=49%; MS (ESI+), 643 (M+H)+.

EXAMPLE 1884-Chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

To a solution of(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride (212 mg, 1.69 mmol) in CH₂Cl₂ (2 ml) was added methylamine(52.0 mg, 6.76 mmol). The mixture was stirred at 22° C. overnight. 1NHCl (1 mL) was added to the mixture, followed by extraction with CH₂Cl₂.The organic layer was dried over Na₂SO₄, filtered, and concentratedunder reduced pressure to afford a colorless oil. This oil was purifiedby prep HPLC to afford4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamidein 84% yield. MS (ESI) 499 (M+1).

EXAMPLE 1894-Chloro-N-[2,5-dichlorophenyl]-N-[4-[(amino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[4-(aminosulfonyl)-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]amino]pentylsulfonylchloride with ammonia. Yield=41%; MS (ESI+), 485 (M+H)+.

EXAMPLE 1904-Chloro-N-[2,5-dichlorophenyl]-N-[4-[(ethylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[4-ethylaminosulfonyl)-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with ethylamine. Yield=37%; MS (ESI+), 513 (M+H)+.

EXAMPLE 1914-Chloro-N-[2,5-dichlorophenyl]-N-[4-[(2-methylpropylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(2-methylpropylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide was preparedanalogous to 4-chloro-N-[2,5-dichlorophenyl]-N-[4[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide by reacting(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with iso-butylamine. Yield=66%; MS (ESI+), 541 (M+H)+.

EXAMPLE 1924-Chloro-N-[2,5-dichlorophenyl]-N-[4-[(dimethylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[4-(dimethylaminosulfonyl)-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with dimethylamine. Yield=65%; MS (ESI+), 513 (M+H)+.

EXAMPLE 1934-Chloro-N-[2,5-dichlorophenyl]-N-[4-[(diethylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[4-(diethylaminosulfonyl)-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with diethylamine. Yield=59%; MS (ESI+), 541 (M+H)+.

EXAMPLE 1944-Chloro-N-[2,5-dichlorophenyl]-N-[[4-[[N-1-methylethyl)methylamino]sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[4-[[N-(1-methylethyl)methylamino]sulfonyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-dichlorophenyl](4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with N-(1-methylethyl)-methylamine. Yield=37%; MS (ESI+), 541(M+H)⁺.

EXAMPLE 1954-Chloro-N-[2,5-dichlorophenyl]-N-[4-[[(N-cyclopentyl)methylamino]sulfonyl]-1(R)-methylbutyl)benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[4-[[N-(cyclopentyl)methylamino]sulfonyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with N-(cyclopentyl)-methylamine. Yield=15%; MS (ESI+), 567(M+H)+.

EXAMPLE 1964-Chloro-N-[2,5-dichlorophenyl]-N-[4-[(1-azetidinyl)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(1-azetidinyl)sulfonyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with azetidine. Yield=24%; MS (ESI+), 526 (M+H)+.

EXAMPLE 1974-Chloro-N-[2,5-dichlorophenyl]-N-[4-[(1-pyrrolidinyl)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(2,5-dichlorophenyl]-N-[4-[(1-pyrrolidinyl)sulfonyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl)-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with pyrrolidine. Yield=61%; MS (ESI+), 539 (M+H)+.

EXAMPLE 1984-Chloro-N-[2,5-dichlorophenyl]-N-[4-[(4-morpholinyl)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(1-morpholinyl)sulfonyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with morpholine. Yield=37%; MS (ESI+), 555 (M+H)+.

EXAMPLE 1994-Chloro-N-[2,5-dichlorophenyl]-N-[4-[(4-thiomorpholinyl)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[4[(4-thiomorpholinyl)sulfonyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with thiomorpholine. Yield=64%; MS (ESI+), 571 (M+H)+.

EXAMPLE 2004-Chloro-N-[2,5-dichlorophenyl]-N-[4-[[(tetrahydro-1,1-dioxido-3-thienyl)amino]sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[2,5-dichlorophenyl]-N-[4-[[(tetrahydro-],1-dioxido-3-thienyl)amino]sulfonyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-dichlorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with tetrahydro-1,1-dioxido-3-thienylamine. Yield=23%; MS(ESI+), 603 (M+H)+.

EXAMPLE 2014-Chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[S-chloro-2-fluorophenyl]-N-[4-(methylaminosulfonyl)-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)methylbutyl]benzenesulfonamideby reacting(4R)-4-[5-chloro-2-fluorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with methylamine. Yield=81%; MS (ESI+), 483 (M+H)+.

EXAMPLE 2024-Chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[(dimethylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[5-chloro-2-fluorophenyl]-N-[4-(dimethylaminosulfonyl)-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[5-chloro-2-fluorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with dimethylamine. Yield=85%; MS (ESI+), 497 (M+H)+.

EXAMPLE 2034-Chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[(1-pyrrolidinyl)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[(1-pyrrolidinyl)sulfonyl]-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[5-chloro-2-fluorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with pyrrolidine. Yield=86%; MS (ESI+), 523 (M+H)+.

EXAMPLE 2044-Chloro-N-[2,5-difluorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[2,5-difluorophenyl]-N-[4-(methylaminosulfonyl)-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-difluorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with methylamine. Yield=86%; MS (ESI+), 467 (M−H)+.

EXAMPLE 2054-Chloro-N-[2,5-difluorophenyl]-N-[4-[(dimethylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[2,5-difluorophenyl]-N-[4-(dimethylaminosulfonyl)-1(R)-methylbutyl]-benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-difluorophenyl][4-chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with dimethylamine. Yield=90%; MS (ESI+), 481 (M+H)+.

EXAMPLE 2064-Chloro-N-[2,5-difluorophenyl]-N-[4-[(1-azetidinyl)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide

4-chloro-N-[2,5-difluorophenyl]-N-[4-[(1-azetidinyl)sulfonyl]-1(R)-methylbutyl]benzenesulfonamidewas prepared analogous to4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamideby reacting(4R)-4-[2,5-difluorophenyl][chlorophenyl)sulfonyl]-amino]pentylsulfonylchloride with azetidine. Yield=50%; MS (ESI+), 493 (M+H)+.

EXAMPLE 207

The general reaction scheme outlined in Scheme 207 is described indetail in the text following the scheme.

To a stirred solution of salicylamide (1.5 g, 11 mmol) in benzene (15mL) at room temperature (room temperature) was addedN-(3-hydroxypropyl)piperidine (1.43 g, 10 mmol), triphenylphosphine(Triphenylphosphine) (2.62 g, 10 mmol) followed bydiethylazodicarboxylate (DEAD), (1.74 g, 10.0 mmol) in benzene (5 mL)over a period of 15 min. The reaction mixture was then left stirred atroom temperature for 40 h, concentrated under reduced pressure. Theresidue was re-dissolved in methylene chloride (DCM; 100 mL). The DCMsolution was washed with 1.0 N NaOH (2×75 mL), water (2×75 mL) andextracted with 1.0 N HCl (3×40 mL). The HCl solution was basified withsolid NaOH to pH 14 to yield a turbid solution that was extracted withDCM (2×50 mL). The combined DCM solution was washed with water (2×50mL), dried with anhydrous MgSO₄, filtered and concentrated under reducedpressure to yield 2.05 g of pale yellow oil (y: 78%). ¹H NMR (300 MHz,CDCl₃) δ (ppm): 8.20 (dd, 1H), 7.9 (br, 1H), 7.44 (m, 1H), 7.05 (t, 1H),7.99 (d, 1H) 6.6 (b, 1H), 4.15, (t, 2H), 2.65-2.27 (m, 6H), 2.05 (p,2H), 1.67-1.54 (m, 2H), 1.45-138 (m, 2H).

To a stirred solution of the above amide (1.5 g, 4.6 mmol) in anhydrousTHF (40 mL) at room temperature was added solid lithium aluminum hydride(lithium aluminum hydride) (473 mg, 11.8 mmol). The reaction mixture washeated at refluxing conditions for 6 h, cooled to room temperature thenquenched with 1.0 N NaOH (0.5 mL). The precipitate was filtered throughcelite and the celite pad was washed with ethyl acetate (30 mL). Thefiltrate was diluted with ethyl acetate (100 mL) and washed with water(2×75 mL), dried with anhydrous MgSO₄, filtered and concentrated to give1.1 g of product as colorless oil (y: 96%). ¹H NMR (300 MHz, CDCl₃) δ(ppm): 7.26-7.20 (m 2H), 6.90-6.86 (m, 2H), 4.02 (t, 2H), 3.84 (s, 3H),2.59-2.43 (m, 6H), 2.06 (d, 2H), 1.68-1.56 (m, 4H), 1.48-1.46 (m, 2H).

To a cooled (0° C., ice bath) solution of the diamine (500 mg, 2.0 mmol)in of DCM (20 mL) was added dry pyridine (164 μL, 2.0 mmol), followed by4-chlorobenzenesulfonylchloride (422 mg, 2.0 mmol). The reaction mixturewas allowed to stir at 0° C. for 2 h then concentrated under reducedpressure. Recrystallization (ethyl acetate/hexanes) of the crude mixtureafforded the desired product as HCl salt. (840 mg of pale yellow solid,y: 99%). ¹H NMR (CDCl₃) δ (ppm): (7.64-7.59 (m, 2H), 7.34-7.26, (m, 2H),7.20, (t, 1H), 7.28-7.24, (m, 1H), 6.86 (m, 1H), 6.61 (d, 1H), 4.10 (t,2H), 4.04 (d, 2H), 3.54 (d, 2H), 3.43 (t, 2H), 2.76-2.72 (m, 2H),2.52-2.43 (m, 2H), 2.20-2.00 (m, 2H), 1.87-1.72 (m 4H).

General Procedure for the Mitsunobu Alkylation of Sulfonamide withAlcohols

To a solution of the sulfonamide (AA) (1.0 mmol) in anhydrous THF (10mL) at room temperature was added Triphenylphosphine (1.5 mmol) followedby the appropriate alcohol (1.5 mmol) and DEAD (1.5 mmol) in that order.The clear reaction mixture was stirred at RT for 24 h then concentratedunder reduced pressure. The crude product was purified by silica gelchromatography (multiple elution, 200 mL of ethyl acetate, 300-500 mL of0.5% triethylamine, 0.5% methanol in ethyl acetate). The desired productwas isolated as a colorless oil (45-65% yield). The free base wasdissolved in DCM to which an excess of a 1.0 M solution of HCl in etherwas added. The resulting solution was concentrated under reducedpressure to give a colorless solid. The HCl salt was purified by passingthrough a short column of silica (10% methanol in DCM) to afford thedesired product in good yield.

The compounds of Examples 208-222 were prepared according to the schemedescribed in the previous example.

EXAMPLE 2084-Chloro-N-(cyclopentylmethyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f) =0.34 (5% methanol, 1% triethylamine in DCM), ¹H NMR (300 MHz,CD₃OD) δ (ppm): 7.82-7.80 (m, 2H), 7.65-7.62 (m, 2H), 7.35 (t, 1H),7.22-7.17 (m, 1H), 6.95-6.90 (m, 2H), 4.31 (s, 2H), 4.14 (t, 2H),3.67-3.45 (m, 4H), 3.03 (t, 2H), 2.36 (d, 2H), 2.44-2.35 (m 2H),2.03-1.84 (m, 5H), 1.66-1.62 (m, 2H), 1.38-1.24 (m, 6H), 0.97-0.96 (m,2H).

EXAMPLE 2094-Chloro-N-(1-methylbutyl-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.34 (5% methanol, 1% triethylamine in DCM), ¹H NMR (300 MHz,CD₃OD) δ (ppm): 7.84-7.82 (m, 2H), 7.62-7.60 (m, 2H), 7.35-7.26 (m, 2H),6.97-6.89 (m, 2H), 4.90 (d, 1H), 4.32 (d, 1H), 4.13 (t, 2H), 3.84 (m,1H), 3.59-3.40 (m, 4H), 3.03-2.96 (m, 2H), 2.36-2.27 (m, 2H), 1.97-1.48(m, 6H), 1.15-0.97 (m, 4H), 0.83 (d, 3H), 0.63 (t, 3H). ¹³C NMR (75 MHz,CD₃OD) δ (ppm) 159.3, 141.0, 138.0, 132.1, 130.6, 130.5, 129.9, 126.6,121.8, 112.3, 66.0, 56.1, 55.4, 54.5, 44.2, 38.6, 25.3, 24.3, 22.8,20.8, 18.2, 14.0. ESI calculated for C₂₆H₃₇ClN₂O₃S [MH+] 493; Observed;493.

EXAMPLE 210N-allyl-4-chloro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.28 (1% triethylamine/5% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ(ppm); 7.64 (m, 2H), 7.40 (m, 2H), 7.09 (in, 1H), 6.95 (m, 1H), 6.71(dt, 2H), 5.14 (m, 1H), 4.65 (d, 2H), 4.22 (s, 2H), 3.90 (t, 2H),3.46-3.16 (m, 6H), 2.80 (m, 2H), 2.06 (m, 2H), 1.78-1.29 (m, 6H).

EXAMPLE 2114-Chloro-N-(2-methyl-2-propenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl)benzenesulfonamideHydrochoride

R_(f) 0.26 (1% triethylamine/5% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ(ppm): 7.62 (m, 2H), 7.41 (m, 2H), 7.08 (m, 1H), 6.91 (dd, 1H), 6.67(dt, 2H), 4.39 (s, 2H), 4.19 (s, 2H), 3.89 (t, 2H), 3.46-3.27 (m, 6H),2.82 (m, 2H), 2.09 (m, 2H), 1.81-1.11 (m, 9H).

EXAMPLE 2124-Chloro-N-(4-nitrobenzyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f) =0.24 (19:1; DCM:methanol). ¹H NMR (CD₃OD) δ (ppm): 7.86-7.81 (m,4H), 7.60 (m, 2H), 7.10-6.99 (m, 4H), 6.66 (t, 1H), 6.48 (d, 1H), 4.33(s, 2H), 4.19 (s, 2H), 3.82 (t, 2H), 3.56-3.45 (mg 4H), 2.98-2.96 (m,2H), 2.24-2.14 (m, 2H), 1.72-1.36 (m, 6H).

EXAMPLE 2134-Chloro-{2-[3-(1-piperidinyl)propoxy]benzyl}-N-(3-pyridinylmethyl)benzenesulfonamidehydrochloride

R_(f)=0.20 (4% methanol, 1% triethylamine in DCM), ¹H NMR (300 MHz,CD₃OD) δ (ppm): 8.25-8.15 (m, 2H), 7.96-7.93 (m, 2H), 7.71-7.68 (m, 2H),7.43 (d, 1H), 7.17-7.11 (m, 3H), 6.81-6.79, (m, 1H), 6.60-6.57 (m, 1H).¹³C NMR (75 MHz, CD₃OD) δ (ppm): 158.5, 148.9, 147.6, 140.7, 138.3,138.1, 133.0, 131.6, 131.0, 130.3, 123.6, 121.8, 111.8, 65.5, 56.1,54.6, 51.7, 50.3, 25.3, 24.4, 22.9.

EXAMPLE 2144-Chloro-N-[(1R)-1-methylbutyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamidehydrochloride

R_(f) 0.28 (4% methanol, 1% triethylamine in DCM), ¹H NMR (300 MHz,CD₃OD) δ (ppm): 7.84-7.82 (m, 2H), 7.62-7.60 (m, 2H), 7.35-7.26 (m, 2H),6.97-6.89 (m, 2H), 4.90 (d, 1H), 4.32 (d, 1H), 4.13 (t, 2H), 3.84 (m,1H), 3.59-3.40 (m, 4H), 3.03-2.96 (m, 2H), 2.36-2.27 (m, 2H), 1.97-1.48(m, 6H), 1.15-0.97 (m, 4H), 0.83 (d, 3H), 0.63 (t, 3H). ¹³C NMR (75 MHz,CD₃OD) δ (ppm): 159.3, 141.0, 138.0, 132.1, 130.6, 130.5, 129.9, 126.6,121.8, 112.3, 66.0, 56.1, 55.4, 54.5, 44.2, 38.6, 25.3, 24.3, 22.8,20.8, 18.2, 14.0. ESI calculated for C₂₆H₃₇ClN₂O₃S [MH+] 493; Observed:493.

EXAMPLE 2154-Chloro-N-[(1S)-1-methylbutyl]-N-[2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.28 (4% methanol, 1% triethylamine in DCM), ¹H NMR (300 MHz,CD₃OD) δ (ppm): 7.84-7.82 (m, 2H), 7.62-7.60 (m, 2H), 7.35-7.26 (m, 2H),6.97-6.89 (m, 2H), 4.90 (d, 1H), 4.32 (d, 1H), 4.13 (t, 2H), 3.84 (m,1H), 3.59-3.40 (m, 4H), 3.03-2.96 (m, 2H), 2.36-2.27 (m, 2H), 1.97-1.48(m, 6H), 1.15-0.97 (m, 4H), 0.83 (d, 3H), 0.63 (t, 3H). ¹³C NMR (75 MHz,CD₃OD) δ (ppm):159.3, 141.0, 138.0, 132.1, 130.6, 130.5, 129.9, 126.6,121.8, 112.3, 66.0, 56.1, 55.4, 54.5, 44.2, 38.6, 25.3, 24.3, 22.8,20.8, 18.2, 14.0. ESI calculated for C₂₆H₃₇ClN₂O₃S [MH+] 493; Observed:493.

EXAMPLE 2164-Chloro-N-(cyclopropylmethyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamidehydrochloride

R_(f)=0.25 (5% methanol, 1% triethylamine in DCM) ¹H NMR (300 MHz,CD₃OD) δ (ppm): 7.84 (d, 2H), 7.62 (d, 2H), 7.30 (dt, 1H), 7.21 (dd,2H), 6.98 (d, 1H), 6.94 (t, 2H), 4.42 (s, 2H), 4.13 (t, 2H), 3.63 (d,2H), 3.51-4.46 (m, 2H), 3.02 (t, 2H), 2.88 (d, 2H), 2.34-2.28 (m, 2H),1.94-1.79 (m, 5H), 1.69-1.49 (m, 1H), 0.61-0.54 (m, 1H), 0.24-0.21 (m,2H), (−)0.12-(−)0.14 (m, 2H). ¹³C NMR (75 MHz, CD₃OD) δ 158.6, 140,139.4, 132.2, 130.9, 130.6, 130.0, 125.1, 121.8, 112.4, 66.0, 56.1,54.4, 53.8, 50.0, 25.3, 24.3, 22.8, 11.28, 4.7. ESI calculated forC₂₅H₃₃ClN₂O₃S [MH+] 477; Observed: 477.

EXAMPLE 2174-Chloro-N-(5-hexynyl-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.19 (1% triethylamine/5% methanol/ethyl acetate) ¹H NMR (300 MHz,CD₃OD) δ (ppm): 7.86-7.83 (m, 2H), 7.66-7.31 (m, 2H), 7.36-7.31 (m, 2H),7.22-7.19 (m, 1H), 7.10-7.09 (m, 1H), 7.00-6.92 (m, 2H), 4.41 (s, 2H),4.15 (t, 2H), 3.33 (m, 2H), 2.99 (m, 2H), 2.34-2.24 5 (m, 2H), 2.17 (t,1H), 1.93-1.68 (m, 8H), 1.22-1.15 (m, 4H). ¹³C NMR (75 MHz, CD₃OD) δ(ppm): 159.1, 140.6, 139.2, 133.0, 131.6, 131.1, 130.5, 125.03, 122.2,112.8, 85.1, 70.3, 66.3, 56.5, 54.9, 50.9, 29.4, 26.9, 25.7, 24.7, 23.2,18.9. ESI calculated for C₂₇H₃₅N₂O₃ClS [MH+] 503: Observed: 503.

EXAMPLE 2184-Chloro-N-(4-methylpentyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f) =0.33 (1% triethylamine/5% methanol/ethyl acetate) ¹H NMR (300MHz, CD₃OD) δ (ppm): 7.86-7.83 (m, 2H), 7.66-7.63 (m, 2H), 7.36-7.31 (m,2H), 7.18 (m, 2H), 7.94 (dt, 2H), 4.36 (s, 2H), 4.14 (t, 2H), 3.67-3.51(m, 4H), 3.07-2.90 (m, 4H), 2.30 (m, 2H), 2.00-1.50 (m, 6H), 0.84 (m,2H), 0.68 (d, 6H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 157.8, 139.3, 138.1,131.8, 130.3, 129.9, 129.3, 123.9, 120.9, 111.5, 55.4, 53.8, 49.7, 48.6,35.9, 27.8, 26.9, 24.6, 23.5, 22.0.

EXAMPLE 2194-Chloro-N-(cyclobutylmethyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f) 038 (1% triethylamine/5% methanol/ethyl acetate) ¹H NMR (300 MHz,CD₃OD) δ (ppm): 7.67 (d, 2H), 7.47 (d, 2H), 7.18-7.01 (m, 2H), 6.82-6.72(m, 2H), 4.13 (s, 2H), 3.95 (t, 2H), 3.47 (m, 2H), 3.33 (m, 2H), 2.83(m, 4H), 2.11 (m, 2H), 1.93-1.07 (m, 13H). ¹³C NMR (75 MHz, CD₃OD) δ158.6, 140.2, 138.7, 132.5, 131.1, 130.7, 130.3, 125.2, 121.8, 112.4,66.0, 56.2, 55.01, 54.7, 51.0, 36.1, 27.1, 25.5, 24.4, 22.9, 18.6. ESIcalculated for C₂₆H₃₅ClN₂O₃S [MH+] 491; Observed: 591.

EXAMPLE 2204-Chloro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}-N-(4-pyridinylmethyl)benzenesulfonamideDihydrochloride

R_(f)=0.23 (5% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.86-7.82(br, 2H), 7.22-7.18 (br, 2H), 6.97-6.89 br, 4H), 6.38-6.32 (br, 2H),6.0-5.83 br, 2H), 4.55 (br, 4H), 3.81-3.65 (m, 4H), 3.35-3.25 (m, 2H),2.97-2.85 (m, 4H), 2.35-2.2.8 (m, 2H), 1.64-1.61 (br, 2H), 1.22-1.06 (m,5H), ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 161.7, 158.5, 142.02, 140.9,137.5, 132.0, 126.9, 123.4, 121.9, 112.1, 66.2, 56.2, 54.9, 54.8, 52.6,52.0, 25.5, 24.4, 22.9.

EXAMPLE 221N-benzyl-4-chloro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.24 (1% triethylamine/5% methanol/ethyl acetate) ¹H NMR (300 MHz,CD₃OD) δ (ppm): 7.64 (d, 2H), 7.40 (d, 2H), 7.05-6.86 (m, 5H), 6.70 (m,2H), 6.58 (t, 1H), 6.47 (d, 1H), 4.19 (s, 2H), 3.98 (s, 2H), 3.68 (t,2H), 3.38 (m, 2H), 3.18 (m, 2H), 2.75 (t, 2H), 1.99 (m, 2H), 1.89-1.14(m, 6H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 159.6, 141.4, 140.3, 139.5,133.8, 132.3, 131.9, 131.4, 130.4, 130.2, 129.4, 125.2, 122.8, 113.3,66.9, 57.5, 55.9, 53.7, 51.5, 26.5, 25.6, 24.0.

EXAMPLE 2224-Chloro-N-(2,3,4,5,6-pentafluorobenzyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.29 (1% triethylamine/5% methanol/ethyl acetate) ¹H NMR (300 MHz,CD₃OD) δ (ppm): 7.91-7.87 (m, 2H), 7.01-7.67 (m, 2H), 7.14 (m, 2H), 6.76(m, 2H), 4.36 (d, 4H), 3.99 (d, 2H), 3.61-3.47 (m, 4H), 3.03 (m, 2H),2.28 (m, 2H), 1.93-1.54 (m, 6H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm):157.9,140.5 137.6 133.3, 130.9 130.6, 130.0, 127.5, 121.2 111.2 65.5, 55.8,54.2, 51.1, 41.5, 24.9, 24.1 22.5. EST calculated for C₂₈H₂₈ClF₅N₂O₃S[MH+] 603; Observed: 603.

EXAMPLE 223

The general reaction scheme outlined in Scheme 223 is described indetail in the text following the scheme.

2-(3′-Piperidinylpropyloxy)-methyl Benzoate

To a solution of methylsalicylate (15.0 g, 98.8 mmol) in dry benzene(300 mL) was added Triphenylphosphine (25.8 g, 98.8 mmol) followed byN-(3-hydroxypropyl)piperidine (14.12 g, 98.8 mmol). The clear reactionmixture was cooled to 0° C. in an ice bath and DEAD (16.5 mL, 108.7mmol) was added in drops over a period of 15 min. The reaction mixturewas slowly warmed to room temperature and left stirred at roomtemperature for 15 h. The reaction mixture was filtered to remove theprecipitated triphenylphosphineoxide and the filtrate was extracted with1.0 M HCl (2×100 mL), the combined HCl solution was basified to pH 9 bythe addition of solid NaHCO₃. The basic solution was extracted withethyl acetate (3×100 mL). The combined ethyl acetate extracts werewashed with saturated brine (2×75 mL), dried with MgSO₄, filtered andconcentrated under reduced pressure to give 20.97 g of pale yellow oil(y: 77%) ¹H NMR (CDCl₃) δ (ppm): 7.70 (dd, 1.8 Hz H), 7.42 (dt, 1.5 Hz,1H), 6.99-6.94 (m, 2H), 4.08 (t, 2H), 3.88 (s, 3H), 2.58-2.45 9m, 6H),2.04 (p, 2H), 1.65-1.60 (in, 4H), 1.47-1.45 (m, 2H).

2-(3′-Piperidinylpropyloxy)-benzylalcohol

To a suspension of lithium aluminum hydride (5.48 g, 144 mmol) inanhydrous THF (500 mL) was added a solution of the methyl ester (20 g,72.1 mmol) in THF (200 mL) over a period of 30 min. The reaction mixturewas refluxed for 6 h, cooled to 0° C. and quenched with water (5.48 mL)followed by 15% NaOH solution (5.48 mL) and finally with water (16.5mL). The crystalline precipitate was filtered through the celite. Thefiltrate was concentrated to yield 18.9 g of crude product which waspurified by chromatography on SiO₂ (2% methanol in CHCl₃) to yield 17.98g of product as white crystalline solid (y: 91%). ¹H NMR (CDCl₃) δ(ppm): 7.27-7.22 (m, 2H), 6.96-6.89 (m, 2H), 4.63 (s, 2H), 4.07 (t,J=2H), 2.55-2.40 (in, 6H), 2.00 (p, 2H), 1.66-1.58 (m, 4H), 1.46-1.43(m, 2H).

The following compounds were similarly prepared.

3-Chloro 6-(3′-piperidinylpropyloxy)-benzylalcohol

2-(3′-Piperidinylpropyloxy)-phenethylalcohol

¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.23-7.12 (m, 2H), 6.90-6.83 (m, 2H),4.05 (t, 214), 3.83 (t, 2H), 2.91 (t, 3H), 2.51-2.47 (m, 6H), 1.99 (p,2H), 1.72-1.58 (m, 4H), 1.48-1.40 (m, 2H).

3-(3′-Piperidinylpropyloxy)-benzylalcohol

2-(3-N,N′-dimethylaminopropyloxy)benzylalcohol

2-(3′-Piperidinylpropyloxy-β-naphthylalcohol

3-(3′-Piperidinylpropyloxy)-2-hydroxymethylpyridine

¹H NMR (300 MHz, CDCl₃) δ (ppm): 8.14 (dd, 1H), 7.20-7.12 (m, 2H), 4.72(s, 2H), 4.05 (t, 3H), 2.51-2.40 (m, 6H), 2.00 (p, 2H), 1.64-1.57 (m,4H), 1.46-1.44 (m, 2H).

2(3-Bromopropyloxy)methylbenzoate

To a stirred solution of methyl salicylate (4.0 g, 26.3 mmol) dry THF(100 mL) under Ar was added Triphenylphosphine (6.9 g, 26.3 mmol)followed by 3-bromopropanol (3.66 g, 26.3 mmol). The rection mixture wascooled to 0° C. in an ice bath and DEAD (4.55 mL, 28.9 mmol) was addedin drops over period of 15 min. The reaction mixture was left to stir atroom temperature for 15 h. The reaction mixture concentrated underreduced pressure. The resulting crude product was purified bychromatography over SiO₂ (10:1, hexanes/ethyl acetate) to give 4.5 g ofthe desired product as a pale yellow oil (y: 63%). ¹H NMR (CDCl₃) δ(ppm): 7.83-7.99 (dd, 1H), 7.49-7.44 (t, 1H), 7.00-6.97 (m, 2H), 4.19(t, 214), 3.89 (s, 3H), 3.71 (t, 2H), 2.36 (p, 2H).

2(3-Pyrrolidinylpropyloxy)methylbenzoate

2(3-Bromopropyloxy)methylbenzoate (4.0 g, 11.3 mmol) was dissolved inneat pyrrolidine (40 mL) and stirred at room temperature for 1 h. Thereaction mixture was then concentrated under reduced pressure. Theisolated residue re-dissolved in DCM and washed with saturatedbicarbonate solution (2×50 mL), dried with MgSO₄, filtered andconcentrated under reduced pressure to give 3.8 g of colorless oil (y:99%) ¹H NMR (CDCl₃) δ (ppm): 7.79-7.77 (d, 1H), 7.47 (t, 1H), 6.99-6.94(m, 2H), 4.11 (t, 2H), 3.89 (s, 2H), 2.67 (t, 2H), 2.57 (br, 4H), 2.06(p, 2H), 1.87 (br, 4H).

2-(3-Pyrrolidinylpropyloxy)benzylalcohol

To a suspension of lithium aluminum hydride (0.9 g, 23.6 mmol) inanhydrous THF (100 mL) was added a solution of the methyl ester (3.0 g11.8 mmol) in THF (10 mL) over a period of 10 min. The reaction mixturewas refluxed for 6 h, cooled to 0° C. and quenched with water (0.9 mL)followed by 15% NaOH solution 0.9 mL) and finally with water (2.7 mLof). The crystalline precipitate was filtered through the celite. Thefiltrate vas concentrated to yield 2.3 g of crude product, which wassubsequently purified by chromatography on SiO₂ (hexanes/ethyl acetate5:1) to afford 2.02 g of product as colorless oil (y: 76%). ¹H NMR(CDCl₃) δ (ppm): 7.26-7.22 (m, 2H), 6.95-6.88 (m, 2H), 4.61 (s, 2H), 4.1(t, 2H), 2.68 (t, 2H), 2.54 (br, 4H), 2.03 (p, 2H), 1.85-1.81 (m, 4H).

General Procedure for the Synthesis of 4-Cholorobenzenesulfanilides

To 1.0 g of amine dissolved in DCM (20 mL) or 1,2-dichloroethane wasadded 1.1 equivalent of pyridine and 1.0 equivalent of4-chlorobenzenesulfonylchloride. The reaction mixture was gentlyrefluxed over night then cooled to room temperature. The reactionmixture was concentrated under reduced pressure and the crude productwas recrystallised from DCM/hexanes to give the product in 90-95% yield.

General Procedure for the Preparation of 4-Cholorobenzenesulfonanilides

To a biphasic mixture of alkylamines (11.0 g) in water (20 mL) was added1.6 equivalent of solid NaHCO₃ followed by 1.0 equivalent of4-chlorobenzesulfonamide. The heterogeneous mixture was refluxed for 2 hthen cooled to room temperature and acidified with 1.0 M HCl to pH 1.The precipitated product was filtered, washed with water andsubsequently recrystallized from ethyl acetate/hexanes to give thecrystalline sulfonamide in 85-95% yield.

General Procedure for Alkylation of 4-Chlorobenzenesulfonamides

To a stirred solution of 2-(3′-piperidinylpropyloxy)-benzylalcohol (1.0equivalent) in THF (10 mL/mmol) was added 1.5 equivalent of PPh₃ and4-chlorobenzenesulfonamides followed by 1.5 equivalent of DEAD. Thereaction mixture was stirred at room temperature for 12 h thenconcentrated under reduced pressure. The crude mixture was purified bychromatography (multiple elution 200 mL of ethyl acetate followed by0.5% methanol 0.5% triethylamine in ethyl acetate) to give 45-60% yieldof product as a colorless oil (free base). The free base was dissolvedin DCM and an excess of a 1.0 M solution of HCl in ether was added. Theresulting solution was concentrated under reduced pressure to give whitesolid. The HCl salt was purified by passing through a short column ofsilica and eluting with 10% methanol in DCM to yield white solid.

The following compounds were prepared according to the scheme describedin the previous example.

EXAMPLE 2244-Chloro-N-[3-(methylsulfanyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f) =0.25 (5% methanol/DCM) ¹H NMR (300 MHz, CDCl₃) 6 μm): 7.87-7.84(m, 2H), 7.63-7.50 (m, 3H), 7.33-7.27 (m, 5H), 6.91 (m, 2H), 6.44 (m,1H), 4.82 (d, 1H), 4.61 (m, 1H), 4.24 (m, 1H), 3.51 (s, 2H), 3.34 (m,4H), 2.41 (t, 4H), 1.66-1.26 (m, 9H), 0.87 (m, 9H).

EXAMPLE 225N-{2-[3-(dimethylamino)propoxy]benzyl}4-nitro-N-phenylbenzenesulfonamide

R_(f)=0.32 (9% methanol/DCM) ¹H NMR (300 MHz, CDCl₃) δ (ppm): 8.36-8.22(m, 3H), 8.06 (m, 1H), 7.80 (m, 2H), 7.23-7.15 (m, 3H), 6.82-6.67 (m,5H), 4.82 (s, 2H), 4.12 (t, 2H), 3.45 (m, 2H), 2.87 (s, 6H), 2.41 (m,2H).

EXAMPLE 226N-{2-[3-(dimethylamino)propoxy]benzyl}-2-nitro-N-phenylbenzenesulfonamide

R_(f)=0.16 (9% methanol/DCM) ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.62 (m,2H), 7.50-7.42 (m, 2H), 7.29-7.07 (m, 7H), 6.85-6.74 (m, 2H), 5.04 (s,2H), 3.86 (t, 2H), 2.42 (t, 2H), 2.25 (s, 6H), 1.85 (m, 2H).

EXAMPLE 2275-(Dimethylamino)-N-{2-[3-(dimethylamino)propoxy]benzyl}-N-phenyl-1-naphthalenesulfonamide

R_(f)=0.16 (9% methanol/DCM) ¹H NMR (300 MHz, CDCl₃) δ (ppm): 8.69-8.23(m, 15H), 4.99 (s, 2H), 4.12 (t, 2H), 3.60 (m, 2H), 2.85 (s, 6H), 2.50(m, 2H).

EXAMPLE 228N-{2-[3-(dimethylamino)propoxy]benzyl}-N-phenylmethanesulfonamide

R_(f)=0.16 (9% methanol/DCM) ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.33-7.15(m, 6H), 6.91-6.70 (m, 3H), 4.88 (s, 2H), 4.06 (t, 2H), 3.36 (t, 2H),2.97 (s, 3H), 2.82 (s, 6H) 2.48-2.37 (m, 2H).

EXAMPLE 2294-Chloro-N-phenyl-N-(2-{2-[3-(1-piperidinyl)propoxy]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.17 (5% methanol, 1% triethylamine) ¹H NMR (300 MHz, CDCl₃) δ(ppm): 7.54-7.47 (m, 4H), 7.36-7.34 (m, 2H), 7.17 (dt, 114), 7.04 (m,2H), 6.92 (m, 2H), 6.75 (t, 1H), 4.17-4.05 (m, 2H), 3.86-3.81 (m, 2H),3.6 (br, 2H), 3.45-3.40 (m, 2H), 3.1 (BR, 2H), 2.79-2.74 (m, 2H),2.34-2.25 (m, 2H), 1.88 (br, 4H), 1.25 (t, 2H). ESI calculated forC₂₈H₃₃ClN₂O₃S (MH⁺) 513, Observed 513.

EXAMPLE 2304-Chloro-N-{5-chloro-2-[3-(1-piperidinyl)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.43 (3:1;1; nBuOH:H₂O:AcOH). ¹H NMR (CDCl₃) δ (ppm): 7.59-7.53(m, 4H), 7.20-7.17 (m, 3H), 7.10 (dd, 1H), 6.90-6.83 (m, 4H), 4.81 (s,2H), 4.08 (t, 2H), 3.56-3.50 (m, 4H), 3.06-3.03 (br, 2H), 2.31-2.26 (m,2H), 1.94-1.80 (m, 6H).

EXAMPLE 2314-Chloro-N-(2,5-difluorophenyl)-N-{5-fluoro-2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.47 (9% methanol in DCM), ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.74(d, 2H), 7.65 (d, 2H), 7.10-8.05 (m, 2H), 6.99-6.89 (m, 2H), 6.85-6.75(m, 2H), 4.83 (s, 2H), 4.11 (t, 2H), 3.41 (m, 2H), 3.21 (br, 2H),2.32-2.23 (m, 2H), 1.87 (m, 4H), 1.58 (br, 2H). LC-MS calculated forC₂₇H₂₈ClF₃N₂O₃S, [MH+] 553; Observed: 553.

EXAMPLE 2324-Chloro-N-(2,5-difluorophenyl)-N-{5-methyl-2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamidehydrochloride

R_(f)=0.45 (9% methanol in DCM), ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.75(d, 2H), 7.66 (d, 2H), 7.05 (m, 3H), 6.81 (m, 3H), 4.76 (s, 2H), 4.03(t, 2H), 3.13-3.00 (m 6H), 2.18 (m, 5H), 1.82 (m, 4H), 1.67 (m, 2H).

EXAMPLE 2334-Chloro-N-(2,5-difluorophenyl)-N-({3-[3-(1-piperidinyl)propoxy]-2-pyridinyl}methyl)benzenesulfonamideHydrochloride

R_(f)=0.33 (10% methanol/DCM) ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.71 (d,1H), 7.63-7.51 (m, 4H), 7.31 (d, 1H), 7.15 (m, 1H), 6.90 (m, 2H), 6.62(m, 1H), 4.87 (s, 2H), 4.08 (t, 2H), 3.28 (m, 2H), 3.07 (m, 4H), 2.21(m, 2H), 1.74 (m, 4H), 1.55 (m, 2H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm):157.1, 146.0, 142.9, 142.5, 139.9, 132.3, 132.1, 129.3, 129.1, 129.0,127.9, 122.2, 121.7, 121.3, 120.3, 120.1, 120.0, 119.8, 58.5, 57.8,56.4, 54.3, 27.2, 26.4, 25.0.

EXAMPLE 2344-Chloro-N-2,5-difluorophenyl-N-({3-[3-(1-piperidinyl)propoxy]-2-naphthylmethyl)benzenesulfonamidehydrochloride

R_(f)=0.55 (9% methanol/DCM) ¹H NMR (500 MHz, CD₃OD) δ (ppm): 7.73-7.67(dd, 4H), 7.63-7.55 (dd, 3H), 7.43 (s, 1H), 7.38 (m, 1H), 7.24 (t, 1H),7.18 (s, 1H), 6.95 (m, 2H), 6.81 (m, 1H), ° C. NMR (125 MHz, CD₃OD) δ(ppm): 160.3, 159.1, 158.4, 156.5, 141.0, 138.5, 136.3, 132.4, 130.8,130.5, 129.7, 128.62, 128.0, 127.7, 125.3, 125.2, 120.0, 119.8, 118.4,118.4, 118.2, 118.2, 107.3, 66.7, 56.7, 55.0, 51.5, 26.0, 25.1, 23.7.

EXAMPLE 2354-Chloro-N-(3-chlorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.13 (1% triethylamine/ethyl acetate) ¹H NMR (300 MHz, CD₃OD) δ(ppm): 7.61 (m, 4H), 7.17 (m, 3H), 6.92-6.84 (m, 4H), 6.67 (t, 1H), 4.84(s, 2H) 4.15 (br, 2H), 3.67 (m, 4H), 3.06 (t, 2H), 2.34 (br, 2H),2.02-1.52 (m, 6H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 156.5, 140.3, 139.4,136.6, 134.0, 130.1, 129.6, 129.2, 129.0, 128.6, 128.0, 127.0, 123.2,120.4, 111.0, 66.4, 56.0, 54.6, 48.7, 26.7, 26.0, 24.4.

EXAMPLE 2364-Chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(1-piperidinyl)propoxy]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.19 (1% triethylamine/ethyl acetate) ¹H NMR (300 MHz, CD₃OD) δ(ppm): 7.66 (dd, 4H), 7.45 (d, 1H), 7.15 (m, 3H), 6.85 (dd, 2H), 7.67(d, 1H), 6.58 (t, 1H), 5.20 (d, 1H), 4.53 (d, 1H), 4.19-4.05 (m, 2H),3.83 (m, 3H), 3.31 (br, 2H), 2.33 (br, 2H), 2.00-1.78 (m, 6H). ¹³C NMR(75 MHz, CD₃OD) δ (ppm): 156.5, 140.3, 139.4, 136.6, 134.0, 130.1,129.6, 129.1, 128.6, 128.0, 127.0, 123.2, 120.4, 111.0, 56.0, 54.6,48.7, 26.7, 26.0, 24.4.

EXAMPLE 237N-(3-bromophenyl)-4-chloro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.59 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.42 (m,2H), 7.45 (m, 1H), 7.22-7.06 (m, 3H), 6.93-6.84 (m, 3H), 6.68 (t, 1H),4.85 (s, 2H), 4.27 (t, 2H), 3.61 (m, 4), 3.07 (br, 2H), 2.34 (m, 2H),1.92 (m, 6H).

EXAMPLE 2384-Chloro-N-[2-(methylsulfanyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.72-7.75 (m, 2H), 7.65-7.59 (m, 2H),7.32-7.10 (m, 3H), 6.97 (dt, 1H), 6.85 (d, 1H), 6.69 (d, 1H), 6.57 (dt,1H), 5.20 (d, 1H), 4.17 (m, 1H), 3.99 (m, 1H), 3.53 (m, 1H), 3.20 (m,4H), 2.23 (m, 2H), 2.12 (s, 3H), 1.91 (m, 4H), 1.65 (br, 2H). ESIcalculated for C₂₈H₃₃ClN₂O₃S₂ [MH+] 545; Observed: 545.

EXAMPLE 2394-Chloro-N-[4-methylsulfanyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.40 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.60 (m,4H), 7.16 (m, 1H), 7.03 (m, 2H), 6.85-6.77 (m, 3H), 6.66 (m, 1H), 4.81(s, 2H), 4.10 (m, 4H), 3.06 (m, 2H), 2.39-2.28 (m, 5H), 2.02-1.1.28 (m,8H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 156.4, 139.1, 138.5, 136.9, 135.8,130.0, 129.1, 129.1, 129.1, 128.8, 126.1, 123.7, 120.4, 111.0, 66.3,56.0, 55.8, 54.6, 48.9, 26.7, 26.0, 25.7, 24.4, 15.3, 14.5, 14.2.

EXAMPLE 2404-Chloro-N-cyclohexyl-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f) 0.49 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.84-7.82(m, 2H), 7.61-7.58 (m, 2H), 7.14-7.25 (m, 2H), 6.97-6.89 (m, 2H), 4.53(s, 2H), 4.15 (m, 2H), 3.63-3.43 (m, 4H), 2.99 (m, 2H), 2.29 (m, 2H),1.98-1.12 (m, 1611). ¹³C NMR (75 MHz, CD₃OD) δ: 158.1, 141.3, 140.0,131.6, 130.7, 130.3, 129.8, 127.1, 121.7, 112.4, 66.1, 59.9, 56.1, 54.5,44.8, 32.4, 27.3, 26.4, 25.3, 24.4, 22.8.

EXAMPLE 2414-Chloro-N-(2-chlorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzenesulfonamideHydrochloride

R_(f)=0.44 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.73-7.69(m, 2H), 7.64-7.59 (m, 2H), 7.30-7.10 (m, 4H), 6.90-6.80 (m, 3H), 6.64(dt, 1H), 5.07 (d, 2H), 4.70 (d, 4H), 4.12-3.99 (d, 2H), 3.52 (m, 1H),3.17 (b, 4H), 2.21 (br, 2H), 1.84 (m, 4H), 1.65 (m, 2H) ¹³C NMR (75 MHz,CD₃OD) δ (ppm): 156.9, 139.0, 138.7, 135.7, 134.8, 133.4, 134.0, 130.3,129.5, 129.3, 129.1, 129.0, 127.0, 123.6, 120.2, 110.9, 66.3, 55.9,54.6, 48.5, 26.5, 26.0, 24.4.

EXAMPLE 2424-Chloro-N-[2-(methylsulfonyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f) 0.13 (0.2% triethylamine/5% methanol/ethyl acetate) ¹H NMR (300MHz, CD₃OD) δ (ppm): 8.07 (dd, 1H), 7.78-7.4 (m, 2H), 7.66-7.45 (m, 1H),7.17 (m, 1H), 6.80 (m, 2H), 6.64 (m, 21H), 5.24 (d, 1H), 4.63 (d, 1H),3.88 (m, 1H), 3.70 (m, 1H), 3.06 (m, 9H), 1.99 (m, 2H), 1.80 (m, 4H),1.63 (m, 2H).

EXAMPLE 2434-Chloro-N-[3-(methylsulfonyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.19 (5% methanol 0.2% triethylamine in ethyl acetate). ¹H NMR(CD₃OD) δ (ppm): 7.78-7.75 (m, 1H), 7.61 (m, 4H), 7.47 (t, 1H), 7.42 (t,1H), 7.35-7.32 (ddd, 1H), 7.17-7.11 (dt, 1H), 7.04-7.01 (dd, 1H), 6.86(d, 1H), 6.71 (dt, 1H), 4.87 (s, 2H), 4.02 (t, 2H), 3.14-3.09 (m, 2H),2.97-2.95 (s overlaps m, 5H), 2.18-2.12 (m, 2H), 1.82-1.74 (m, 4H),1.62-1.60 (m, 2H).

EXAMPLE 2444-Chloro-N-[4-(methylsulfonyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.18 (93:5:2; ethyl acetate:methanol:triethylamine). ¹H NMR (300MHz, CD₃OD) δ :7.79 (d, 2H), 7.62 (m, 4H), 7.27-7.14 (m, 3H), 6.96-6.88(m, 2H), 6.69 (m, 1H), 4.9 (s overlapped by HOD), 2H), 4.12 (m, 2H),3.70-3.59 (m, 4H), 3.07-3.01 (m overlaps s, 5H), 2.29 (m, 2H), 2.02-1.78(m, 6H). ESI calculated for C₂₈H₃₃ClN₂O₅S₂: 576. Observed 577 (MH⁺).

EXAMPLE 2454-Chloro-N-[3-(methylsulfanyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamidehydrochloride

¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.62 (m, 4H), 7.32-7.05 (m, 3H),6.95-6.82 (m, 2H), 6.92-6.61 (m, 3H), 4.84 (s, 2H), 4.14 (t, 2H), 3.58(m, 4H), 3.05 (m, 2H), 2.28 (m, 5H), 1.88 (br, 6H). ESI calculated forC₂₈H₃₃ClN₂O₃S₂ [MH+] 545; Observed: 545.

EXAMPLE 2464-Chloro-N-(2,3-dihydro-1H-inden-2-yl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.24 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.91-7.87(m, 2H), 7.64-7.61 (m, 2H), 4.78 (m, 1H), 7.21 (m, 1H), 7.05-0.90 (m,5H), 6.83 (d, 1H), 4.88 (m, 1H), 4.43 (s, 2H), 3.88 (t, 2H), 3.30 (m,2H), 2.88-2.59 (m, 10H), 1.67-1.50 (m, 6H). ¹³C NMR (75 MHz, CD₃OD) δ(ppm): 157.1, 141.4, 140.8, 140.3, 130.8, 130.3, 130.2, 129.7, 127.9,127.5, 125.3, 121.7, 112.01, 66.8, 60.0, 56.8, 55.2, 43.6, 37.2, 26.6,25.8, 24.4.

EXAMPLE 247N-(4-bromophenyl)-4-chloro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.18 (19:1 DCM:methanol) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.71 (m,4H), 7.33 (m, 2H), 7.17 (m, 1H), 6.91-6.81 (m, 4H), 6.69 (m, 1H), 4.82(s, 2H), 4.10 (t, 2H), 3.56 (m, 2H), 3.23 (m, 4H), 2.28 (m, 2H), 1.86(m, 4H), 1.66 (br, 2H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 158.5, 140.7,138.9, 137.8, 133.1, 132.2, 131.1, 130.7, 130.6, 124.0, 122.9, 121.5,112.3, 66.2, 56.4, 54.9, 54.9, 51.4, 25.7, 24.8, 23.2.

EXAMPLE 2484-Chloro-N-(5-chloro-2-hydroxyphenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl)benzenesulfonamideHydrochloride

R_(f) =0.62 (10% methanol/DCM), ¹H NMR (300 MHz, CD₃OD) δ (ppm):7.68-7.65 (m, 2H), 7.56-7.53 (m, 2H), 7.21-7.16 (m, 1H), 7.0 (dd, 1H),6.92-6.87 (m, 2H), 6.76 (d, 1H), 6.67 (t, 1H), 6.56 (d, 1H), 4.93 (s,2H), 4.15 (t, 2H), 3.72-3.60. (m, 4H), 3.12-3.10 (m, 2H), 2.39-2.30 (m,2H), 2.04-1.73 (m, 5H), 1.61-1.52 (m, 1H). ¹³C NMR (75 MHz, CD₃OD) δ(ppm): 158.4, 155.4, 140.2, 139.6, 133.9, 132.7, 131.1, 130.7, 130.4,130.2, 125.9, 124.5, 124.1, 121.5, 118.2, 112.1, 65.9, 56.2, 54.7, 25.5,24.5, 22.9.

EXAMPLE 2494-Chloro-N-(2,3-dihydro-1H-inden-1-yl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.40 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.89 (m,2H), 7.60 (m, 2H, 7.31 (d, 1H), 7.23-7.07 (m, 3H), 6.91 (m, 1H), 6.80(t, 1H), 6.71 (d, 1H), 6.56 (d, 1H), 5.57 (t, 1H), 4.49 (d, 1H), 4.12(m, 1H), 3.80 (t, 2H), 2.86-2.45 (m, 8H), 2.17 (m, 1H), 1.91-1.70 (m,3H), 1.66-1.49 (m, 6H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 157.6, 145.2,141.3, 140.8, 140.2, 130.8, 130.7, 130.1, 129.6, 129.36, 127.4, 127.1,126.1, 125.8, 121.3, 111.8, 67.0, 65.0, 57.1, 55.5, 43.8, 31.5, 31.0,27.0, 26.3, 25.0.

EXAMPLE 2504-Chloro-N-cyclopentyl-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.60 (9:1; DCM:methanol) ¹H NMR (300 MHz CD₃OD) δ (ppm): 7.84 (m,2H), 7.73-7.62 (m, 2H), 7.37 (d, 1H), 7.25 (m, 1H), 6.93 (m, 2H), 4.45(s, 2H), 425 (m, 2H), 4.11 (t, 2H), 2.28 (m, 2H), 2.00-1.71 (m, 4H),1.56-0.87 (m, 10H). ¹³C NMR (75 MHz, CD₃OD) δ ppm): 157.2, 140.8, 140.0,133.2, 133.06, 130.6, 130.5, 130.1, 130.0, 129.8, 127.6, 121.8, 112.2,66.1, 60.8, 55.9, 54.5, 44.2, 29.86, 25.3, 24.4, 22.8.

EXAMPLE 2514-Chloro-N-(2,4-dichlorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.31 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.65-7.52(m, 4H) 7.28 (d, 1H) 7.14-7.07 (m, 2H), 6.79 (m, 3H), 6.60 (t, 1H), 4.96(m, 1H), 4.60 (m, 1H), 4.00 (m, 2H), 3.34-3.03 (m, 6H), 2.10 (m, 2H),1.73 (m, 4H), 1.55 (m, 2H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 160.34,142.46, 140.79, 139.54, 137.77, 137.42, 136.15, 134.59, 132.99, 132.84,132.39, 132.26, 130.38, 125.17, 123.08, 113.86, 67.96, 58.22, 56.55,52.47, 27.56, 26.65, 25.19.

EXAMPLE 2524-Chloro-N-(2,5-dibromophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.26 (10%° methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm):7.64-7.53 (m, 4H), 7.31 (d, 1H), 7.21 (dd, 1H), 7.10 (dt, 1H), 6.86 (d,1H), 6.79 (d, 1H), 6.61 (t, 1H), 5.40 (d, 1H), 4.58 (d, 1H), 3.95 (m,2H), 3.22-2.02 (m, 6H), 2.08 (m, 2H), 2.11-1.54 (m, 6H). ¹³C NMR (75MHz, CD₃OD) δ (ppm): 154.6, 136.9, 135.6, 134.4, 132.0, 130.2, 129.0,127.4, 126.7, 126.7, 122.5, 118.9, 117.4, 117.33, 108.0, 61.7, 52.2,50.6, 50.5, 21.3, 20.3, 18.7. ESI calculated for C₂₇H₂₉Br₂ClN₂O₃S [MH+]657; Observed: 657.

EXAMPLE 2534-Chloro-N-(2,5-dichlorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.35 (10% methanol/CDCl₃) ¹H NMR (300 MHz, CD₃OD), δ (ppm):7.72-7.60 (m, 4H), 7.27-7.15 (m, 3H), 6.87 (m, 2H), 6.78 (dd, 1H), 6.63(t, 1H) 5.03 (d, 1H), 5.68 (d, 1H), 4.15 (m, 1H), 4.02 (m, 1H) 3.67 (m,1H) 3.65 (m, 1H), 2.31 (m, 2H), 1.88 (m, 6H). ¹³C NMR (75 MHz, CD₃OD) δ(ppm): 158.69, 141.00, 138.84, 137.78, 135.68, 133.50, 133.39, 133.02,132.61, 131.54, 131.27, 130.82, 130.70, 123.27, 121.54, 112.23, 65.98,56.28, 54.66, 51.00, 25.44, 24.42, 22.93.

EXAMPLE 2544-Chloro-N-cycloheptyl-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.37 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.65 (d,2H), 7.41 (d, 2H), 7.29 (d, 1H), 7.06 (t, 1H), 6.76 (m, 2H), 4.26 (s,2H), 3.88 (t, 2H), 3.67 (m, 1H), 2.54-2.40 (m, 6H), 1.88 (m, 2H),1.49-1.12 (m, 18H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 158.2, 141.9,140.6, 131.7, 131.3, 130.6, 130.4, 128.5, 122.3, 112.9, 68.1, 62.6,58.0, 56.2, 44.0, 35.3, 29.2, 28.0, 27.1, 27.0, 25.6.

EXAMPLE 2554-Chloro-N-(2-chloro-3-pyridinyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.37 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.77-7.73(4H, m), 7.33-7.20 (3H, m), 6.94-6.90 (m, 3H), 6.75-6.70 (m, 1H), 5.03(d, 1H), 5.77 (d, 1H), 4.13-4.02 (m, 2H), 3.44-3.16 (m, 6H), 2.24 (m,2H), 1.89-1.84 (m, 4H), 1.67 (m, 2H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm):159.1, 141.0, 139.3, 138.6, 135.2, 133.4, 131.6, 131.6, 131.1, 134.0,129.4, 127.8, 123.7, 121.6, 112.4, 66.1, 56.7, 54.9, 54.9, 51.6, 25.7,24.7, 23.2.

EXAMPLE 256N-[(2S)-bicyclo[2.2.1]hept-2-yl]4-chloro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.33 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.86-7.81(m, 2H), 7.62-7.58 (m, 2H), 7.49 (m, 1H), 7.19 (m, 1H), 6.93 (m, 2H),4.44 (s, 2H), 4.03 (m, 2H), 3.89 (m, 1H), 2.62 (m, 6H), 2.07-0.90 (m,18H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 158.2, 1423, 141.5, 132.1, 131.5,131.3, 130.79, 129.4, 123.0, 113.5, 68.6, 64.2, 58.6, 56.9, 44.9, 43.5,40.0, 38.6, 38.5, 31.8, 29.9, 28.66, 27.6, 26.3.

EXAMPLE 2574-Chloro-N-(3,5-dichlorophenyl)-N-(2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.6 (10% methanol/DCM) ¹H NMR (500 MHz, CDCl₃) δ (ppm): 7.65 (m,4H), 7.30 (t, 1H), 7.23-7.18 (m, 1H), 6.98-6.92 (m, 4H), 6.73 (m, 1H),4.15 (t, 2H) 3.64-3.57 (m, 2H), 3.70-3.67 (m, 2H), 3.09-3.04 (m, 2H),2.38-2.32 (m, 2H), 2.10-1.98 (m, 2H), 1.88-1.79 (m, 4H) ESI calculatedfor C₂₇H₂₉Cl₃N₂O₃S [MH+] 569; Observed: 569.

EXAMPLE 2584-Chloro-N-(2,5-dichloro-3-pyridinyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f) =0.49 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 8.28 (d,1H), 7.77-7.54 (m, 4H), 7.41 (d, 1H), 7.23 (m, 1H), 6.93-6.86 (m, 2H),6.71 (m, 1H), 5.05 (m, 10H), 4.78 (m, 1H), 4.17-4.04 (m, 2H), 3.69-3.44(m, 4H), 3.04 (m, 2H), 2.31 (m, 2H), 2.00-1.51 (m, 6H). ESI calculatedfor C₂₆H₂₈Cl₃N₃O₃S [MH+] 568; Observed: 568.

EXAMPLE 259N-{5-[(2,5-dichloro{2-[3-(1-piperidinyl)propoxy]benzyl}anilino)sulfonyl]-4-methyl-1,3-thiazol-2-yl}acetamideHydrochloride

R_(f)=0.70 (3:1:1 n-BuOH/H₂O/AcOH) ¹H NMR (500 MHz, DMSO) δ (ppm): 12.73(s, 1H), 10.08 (br, 1H), 7.43 (m, 2H), 7.27 (d, 1H), 7.20 (m, 1H), 6.99(d, 1H), 6.91 (d, 1H), 6.75 (t, 1H), 4.99 (d, 1H), 4.69 (d, 1H), 4.00(m, 2H), 3.47-3.22 (m, 1H), 2.21-1.70 (m, 9H). ESI calculated forC₂₇H₃₂Cl₂N₄O₄S [MH+] 611; Observed: 611.

EXAMPLE 260(E)-N-(2,5-dichlorophenyl)-2-phenyl-N-{2-[3-(1-piperidinyl)propoxy]benzyl}ethenesulfonamidehydrochloride

R_(f)=0.62 (3:1:1 n-BuOH/H₂O/AcOH) ¹H NMR (500 MHz, CD₃OD) δ (ppm): 7.62(m, 2H), 7.45 (m, 3H), 7.35-7.32 (dd, 2H), 7.29-7.21 (m, 4H), 6.93 (m,2H), 6.72 (t, 1H), 4.88 (m, 2H), 4.17 (m, 1H), 4.04 (m, 1H), 3.39 (m,6H), 2.27 (m, 2H), 1.93 (m, 4H), 1.69 (m, 2H). ESI calculated forC₂₉H₃₂Cl₂N₂O₃S [MH+] 559; Observed: 559.

EXAMPLE 261N-(2,5-dichlorophenyl)(phenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}methanesulfonamideHydrochloride

R_(f)=0.67 (3:1:1 n-BuOH/H₂O/AcOH) ¹H NMR (500 MHz, CD₃OD) δ (ppm):7.39-7.28 (m, 8H), 6.96 (m, 2H), 6.80 (t, 2H), 4.88 (m, 2H), 4.51 (s,2H), 4.05 (d, 2H), 3.31-3.30 (m, 6H), 2.18 (m, 2H), 1.78 (m, 4H), 1.61(br, 2H). ESI calculated for C₂₈H₃₂Cl₂N₂O₃S [MH+] 547; Observed: 547.

EXAMPLE 262N-(2,5-difluorophenyl)-4-methyl-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.62-7.50 (m, 3H), 7.37 (m, 2H), 7.13(t, 1H), 6.93-6.84 (m, 2H), 6.76 (d, 1H), 6.63-6.58 (m, 2H), 4.71 (s,2H), 4.12-4.05 (m, 2H), 3.63-3.57 (m, 2H), 3.03 (t, 2H), 2.42 (s, 3H),2.30 (m, 2H), 1.97-1.68 (m, 6H).

EXAMPLE 2634-Bromo-N-(2,5-difluorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.79 (d, 2H), 7.63 (d, 2H), 7.19 (t,1H), 7.00 (m, 2H), 6.90 (d, 1H), 6.85 (d, 1H), 6.73 (m, 1H), 6.65 (m,1H), 4.83 (s, 2H), 4.15 (m, 2H), 3.68 (d, 2H), 3.60 (m, 2H), 3.30 (m,2H), 3.06 (m, 2H), 2.35 (m, 2H), 1.99 (m, 2H), 1.85 (m, 3H), 1.55 (m,1H).

EXAMPLE 2644-Chloro-N-cyclopropyl-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.32 (10% methanol/DCM) ¹H NMR (500 MHz, CD₃OD) 8 μm): 7.88-7.86(d, 2H), 7.67-7.65 (d, 2H), 7.31-7.22 (m, 2H), 6.96-6.88 (dt, 2H), 4.38(s, 2H), 4.11 (s, 2H), 3.31 (s, 1H), 20 (m, 4H), 2.27-2.22 (m, 2H),1.87-1.78 (m, 6H), 1.66 (m, 2H), 0.47 (m, 4H). ¹³C NMR (125 MHz, CD₃OD)δ (ppm): 158.4, 140.6, 137.5, 133.0, 130.8, 130.8, 130.7, 125.5, 121.7,112.4, 66.2, 56.3, 54.8, 52.2, 31.86, 25.7, 24.7, 23.2.

EXAMPLE 265N-[(2S)-bicyclo[2.2.1]hept-2-yl]-4-chloro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.52 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.81 (m,2H), 7.56 (m, 2H), 7.39 (d, 1H), 7.19 (m, 1H), 6.91 (m, 2), 4.46 (s,2H), 4.02 (t, 2H), 3.85 (m, 2H), 2.55 (m, 7H), 2.01 (m, 3H), 1.68-0.99(m, 14H). ESI calculated for C₂₈H₃₁ClN₂O₃S [MH+] 517; Observed: 517.

EXAMPLE 2664-Chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.38 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.69-7.58(m, 4H), 7.18-6.61 (m, 7H), 4.79 (s, 2H), 4.12 (t, 2H), 3.68-3.56 (m,4H), 3.07-2.99 (m, 2H), 2.33 (m, 2H), 1.98-1.52 (m, 6H). ¹³C NMR (75MHz, CD₃OD) δ (ppm): 158.6, 141.0, 138.3, 132.9, 131.5, 130.8, 130.5,127.5, 127.5, 123.4, 121.6, 120.0, 119.7, 118.6, 118.5, 118.4, 118.3,1182, 118.1, 112.3, 66.0, 56.3, 54.7, 51.2, 51.1, 25.5, 24.5, 22.9.

EXAMPLE 2674-Chloro-N-(2-methylphenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.59 (15% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.74-7.65(m, 4H), 7.24-6.93 (m, 5H), 6.60-6.55 (dd, 3H), 5.47 (d, 1H), 4.14 (m,4H), 3.80-3.43 (m, 6H), 3.34 (m, 2H), 1.90-1.72 (m, 6H). ¹³C NMR (75MHz, CD₃OD) δ (ppm): 158.7, 141.9, 140.7, 138.5, 138.3, 133.5, 132.1,131.1, 130.8, 130.61, 129.6, 128.9, 127.3, 123.6, 121.3, 111.9, 65.8,56.2, 54.6, 52.5, 25.5, 24.5, 22.9, 18.5. ESI calculated forC₂₈H₃₃ClN₂O₃S [MH+] 513; Observed: 513.

EXAMPLE 2684-Chloro-N-(3-methylphenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.32 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.71-7.49(m, 4H), 7.20-6.94 (m, 4H), 6.84 (d, 1H), 6.69 (m, 3H), 4.80 (s, 2H),4.04 (t, 2H), 3.22 (m, 2H), 3.06 (b, 4H), 2.29-2.17 (m, 5H), 1.80 (m,4H), 1.61 (m, 2H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 156.5, 138.5, 138.1,137.8, 136.4, 130.7, 129.1, 128.8, 128.7, 128.6, 128.0, 127.8, 125.2,122.7, 119.5, 110.4, 64.6, 54.7, 53.0, 49.3, 24.2, 23.2, 21.8, 19.4. ESIcalculated for C₂H₃₃ClN₂O₃S [MH+] 513; Observed: 513.

EXAMPLE 2692-{2-[3-(1-piperidinyl)propoxy]benzyl}-2H-naphtho[1,8-cd]isothiazole1,1-Dioxide Hydrochloride

R_(f)=0.48 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ μm): 8.11-7.97(dd, 2H), 7.76 (m, 1H), 7.44-7.23 (m, 4H), 6.98 (d, 1H), 6.87 (t, 1H),6.68 (m, 1H), 4.95 (s, 2H), 4.10 (t, 2H), 2.60-2.41 (m, 6H), 2.02 (m,2H), 1.57-1.40 (m, 6H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 160.1, 140.2,134.8, 134.4, 134.0, 133.0, 132.8, 132.7, 131.8, 126.8, 124.1, 123.1,121.8, 114.7, 107.4, 69.1, 58.9, 57.2, 44.2, 28.6, 27.6, 26.2. ESIcalculated for C₂₅H₂₈ClN₂O₃S [MH+] 437; Observed: 437.

EXAMPLE 2704-Chloro-N-(2,3-dichlorophenyl)-N-(2-[3-(1-piperidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.38 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) 3 μm): 7.73-7.62(m, 4H), 7.42 (dd, 1H), 7.22-7.10 (m, 2H) 6.85 (d, 1H) 6.83 (dd, 1H),6.73 (dd, 1H) 6.63 (t 1H) 5.16 (d, 1H) 4.58 (d, 1H) 4.18 (m, 1H) 4.05(d, 1H) 3.53-3.30 (m, 6H) 2.36-1.90 (m, 4H). ¹³C NMR (75 MHz, CD₃OD) δ(ppm): 159.39 141.58, 139.54, 139.42, 136.60, 135.47, 133.69, 132.59,132.31, 132.15, 131.48, 131.38, 129.32, 123.92, 122.10, 112.87, 66.59,56.95, 55.31, 51.84, 26.10, 25.07, 23.59. ESI calculated forC₂₇H₂₉Cl₃N₂O₃S [MH+] 567; Observed: 567.

EXAMPLE 2714-Chloro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}-N-tetrahydro-2H-pyran-4-ylbenzenesulfonamidehydrochloride

R_(f)=0.42 (10% methanol/DCM), ¹H NMR (300 MHz, CD₃OD) δ (ppm):7.90-7.86 (m, 2H), 7.63-7.69 (m, 2H), 7.41-7.39 (m, 1H), 7.33-7.27 (m,1H), 6.97-6.92 (m, 2H), 4.56 (s, 2H), 4.16-4.12 (t, 2H), 3.93-3.87 (m,1H), 3.80-3.73 (m, 2H), 3.44 3.22 (m, 8H), 2.32-227 (m, 2H), 1.89-1.80(m, 4H), 1.61-1.53 (m 4H), 1.29-1.25 (m, 2H). ¹³C NMR (free base, 75MHz, CDCl₃) δ (ppm): 155.1, 139.5, 138.4, 128.9, 128.6, 127.9, 125.6,120.0, 110.2, 55.7, 55.1, 54.2, 41.0, 30.8, 26.4, 25.4, 23.9, 14.0.

EXAMPLE 2724-Chloro-N-(2,5-difluorophenyl)-N-({1-[3-(1-piperidinyl)propoxy]-2-naphthylmethyl)benzenesulfonamideHydrochloride

R_(f)=0.6 (10:1 DCM:methanol), ¹H NMR (CD₃OP) δ (ppm): 7.99-7.96 (m,1H), 7.82-7.76 (m, 3H), 7.66-7.63 (m, 1H), 7.54-7.45 (m, 3H), 7.30-7.28(m, 1H), 7.05-7.00 (m, 2H), 6.84-6.81 (m, 1H), 5.01-4.91 (m, 2H),4.04-4.01 (m, 2H), 3.32-3.00 (m, 6H), 2.23-2.26 (m, 2H), 1.81-1.64 (m,6H). LC-MS calculated for C₃₁H₃₁ClF₂N₂O₃S: 585: observed 585.

EXAMPLE 2734-Chloro-N-(2,5-difluorophenyl)-N-({1-[3-(1-piperidinyl)propoxy]-2-naphthyl}methyl)benzenesulfonamideHydrochloride

Mp=228° C. (d). R_(f)=0.45 (10:1; DCM:methanol). ¹H NMR (DMSO) δ (ppm):8.20-8.17 (m, 1H), 7.87-7.77 (m, 6H), 7.55-7.11 (m, 5H), 6.57 (m, 1H),5.25 (m, 2H), 3.95 (m, 2H), 3.40-3.36 (m, 2H), 3.15 (m, 2H), 2.85 (m,2H), 2.12 (m, 2H), 1.80-1.76 (m, 4H), 1.42 (m, 2H). LC-MS calculated forC₃₁H₃₁ClF₂N₂O₃S: 585: observed 585.

EXAMPLE 274

Using the general synthetic scheme outlined in SCHEME 274, compoundsdescribed in Examples 275-283 were prepared.

EXAMPLE 2754-Chloro-N-(2,5-difluorophenyl)-N-(2-hydroxybenzyl)benzenesulfonamide

R_(f)=0.50 (3:1; hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.74-7.71 (d, 2H, 7.54-7.51 (d, 2H), 7.20-6.96 (m, 1H), 7.00-6.96 (m,2H), 6.89-6.87 (m, 2H), 6.75-6.67 (m, 2H), 6.45 (s, 1H), 4.70 (s, 2H).

EXAMPLE 2764-Chloro-N-{2-[2-(1-methyl-2-piperidinyl)ethoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.23 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.66-7.60(m, 4H), 7.22-7.15 (m, 4H), 6.95-6.89 (m, 4H), 6.68 (t, 1H), 5.04 (d,1H), 4.71 (d, 1H), 4.16 (m, 2H), 3.85 (m, 1H), 3.47 (d, 1H), 3.19 (m,1H), 2.98 (s, 3H), 2.65 (m, 1H), 2.22 (m, 1H), 2.01-1.64 (m, 6H). ¹³CNMR (75 MHz, CD₃OD) δ (ppm): 158.7, 140.9, 140.0, 138.4, 133.3, 131.2,131.0, 130.9, 130.7, 130.3, 130.0, 124.7, 121.9, 112.7, 64.9, 63.4,57.4, 51.8, 41.1, 31.5, 28.9, 24.5, 23.1. ESI calculated forC₂₇H₃₃ClN₂O₃S [MH+] 499; Observed: 499.

EXAMPLE 2774-Chloro-N-{2-[2-(1-methyl-2-pyrrolidinyl)ethoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.24 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.62 (m,4H), 7.22-7.16 (m, 4H), 6.96-6.89 (m, 4H), 6.68 (t, 1H), 4.51 (d, 1H),4.77 (d, 1H), 4.28 (m, 2H), 4.14-4.02 (m, 2H), 3.73 (m, 1H), 3.22 (m,1H), 3.04 (s, 3H), 2.69-2.44 (m, 2H), 2.28-1.91 (m, 4H). ¹³C NMR (75MHz, CD₃OD) δ (ppm): 158.6, 140.8, 139.9, 138.4, 133.4 131.2, 130.9,130.9 130.7, 130.3, 129.7-124.7, 121.9, 112.7, 67.8, 65.9, 57.8, 51.8,40.1 31.6 30.5, 22.7.

EXAMPLE 2784-Chloro-N-phenyl-N-{2-[2-(2-piperidinyl)ethoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.40 (14% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.59-7.52(m, 4H), 7.15-7.08 (m, 4H), 6.88-6.80 (m, 4H), 6.60 (t, 1H), 4.93 (d,1H), 4.68 (d, 1H) 4.15-4.05 (m, 2H), 3.79 (m, 1H), 3.37 (m, 1H), 3.10(m, 1H), 2.26-1.49 (m, 8H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 158.6,140.8, 140.1, 138.5, 133.1, 131.1, 131.0, 130.9, 130.7, 130.4, 129.7,124.9, 121.9, 112.9, 64.9, 55.9, 51.8, 46.6, 34.9, 29.9, 23.9, 23.5. ESIcalculated for C₂₆H₂₉ClN₂O₃S [MH+] 485; Observed: 485.

EXAMPLE 279N-{2-[3-(3-hydroxy-1-pyrrolidinyl)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.15 (9% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.52-7.46(m, 4H), 7.10-7.01 (m, 4H), 6.80-6.73 (m, 4H), 6.54 (m, 1H), 4.74 (s,2H), 4.48-4.46 (m, 1H), 4.02 (t, 2H), 3.58 (m, 3H), 3.39 (m, 3H),2.28-1.93 (m, 4H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 160.3, 142.4, 141.6,140.1, 134.8, 132.8, 132.5, 132.4, 131.9, 131.3, 126.4, 123.4, 114.3,72.4, 67.9, 64.9, 56.9, 55.9, 53.5, 36.0, 29.2. ESI calculated forC₂₇H₂₉ClN₂O₄S [MH+] 501; Observed: 501.

EXAMPLE 2804-Chloro-N-{2-[3-(2-ethyl-1-piperidinyl)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.23 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.44-7.59(m, 4H), 7.24-7.15 (m, 4H), 6.94-6.89 (m, 4H), 6.68 (t, 1H), 4.88 (d,2H), 4.17 (t, 2H), 3.66-3.52 (d, 3H), 3.25 (m, 2H), 2.33 (m, 2H),2.03-1.63 (m, 8H), 1.05 (t, 3H), ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 158.9,141.0, 140.2, 138.9, 133.4, 131.3, 131.1, 131.0, 130.5, 129.8, 125.0,122.1, 113.0, 66.9, 65.6, 52.0, 51.9, 51.7, 28.2, 25.8, 24.2, 22.4,10.8. ESI calculated for C₂₉H₃₅ClN₂O₃S [MH+] 527; Observed: 527.

EXAMPLE 2814-Chloro-N-phenyl-N-[2-(4-pyridinylmethoxy)benzyl]benzenesulfonamideHydrochloride

R_(f)=0.63 (5% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 8.31 (d,2H), 7.47-7.38 (m, 4H), 7.25 (d, 2H), 7.11 (m, 1H), 7.02-6.97 (m, 4H),6.79 (m, 2H), 6.70 (m, 2H), 4.90 (s, 2H), 4.77 (s, 2H).

EXAMPLE 2824-Chloro-N-phenyl-N-[2-(2-pyridinylmethoxy)benzyl]benzenesulfonamideHydrochloride

R_(f)=0.57 (5% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 8.87 (d,1H), 9.60 (t, 1H), 8.17 (d, 1H), 8.02 (t, 1H), 7.61 (q, 4H), 7.29-6.86(m, 9H), 5.47 (s, 2H), 5.00 (s, 2H), ¹³C NMR (75 MHz, CD₃OD) δ (ppm):156.2, 153.8, 147.5, 143.6, 140.5, 138.3, 136.9, 134.1, 130.6, 130.5,130.4, 130.0, 129.3, 127.4, 126.8, 125.7, 123.1, 113.5, 68.7, 51.3. ESIcalculated for C₁H₁₁ClN₂O₃S [MH+) 465; Observed: 465.

EXAMPLE 2834-Chloro-N-phenyl-N-[2-(3-pyridinylmethoxy)benzyl]benzenesulfonamideHydrochloride

R_(f)=0.61 (5% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 8.58-8.51(m, 2H), 7.89, (d, 1H), 7.62-7.44 (m, 5H), 7.30 (dd, 1H), 7.20-7.16 (m,4H), 6.98-6.84 (m, 4H), 5.07 (s, 2H), 4.90 (s, 2H).

EXAMPLE 284

The general synthetic scheme set forth in SCHEME 284 can also be usedfor the preparation of numerous compounds according to the invention.

2-[(ω-Bromo Alkyloxy) N-benzyl)4-chlorobenzenesulfanilides

To a stirred suspension of lithium aluminum hydride (1.78 g, 46.8 mmol)in THF (90 mL) at 0° C. was added a solution of salicylanilide (5.0 g,23.4 mmol) in THF (50 mL) over 0.5 h. The resulting mixture was heatedat refluxing for 3 h, then cooled to 0° C., quenched with saturatedNaHSO₄ solution, filtered through celite pad and the celite pad waswashed with ethyl acetate. The filtrate was diluted with ethyl acetate(300 mL), washed with saturated brine (2×100 TL), dried with MgSO₄,filtered and concentrated under reduced pressure to give 3.9 g of thedesired product as white solid (y: 83%) R_(f)=0.40 (25% ethylacetate/hexanes) ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.28-7.15 (m, 4H),7.95-6.84 (in, 5M), 4.41 (s, 2H).

Sulfonylation of the amine (2.0 g, 10.0 mmol) according to the generalprocedure described elsewhere provided the desired product (3.40 g, 9.10mmol, 91%). R_(f)=0.35 (25% ethyl acetate/hexanes) ¹H NMR (300 MHz,CDCl₃) δ (ppm): 7.66-7.49 (m, 4H), 7.28-7.14 (m 4H), 6.97-6.65 (m, 5H),4.71 (s, 21).

General Procedure for Alkylation of Phenol with ω-Bromoalkanols

Mitsunobu alkylation of phenol with 3-bromo propanol, 4-bromo butanoland 5-bromo pentanol according general procedure described elsewheregave the corresponding 2-[(O-bromo alkyloxy)N-benzyl]4-chlorobenzenesulfanilides.

General Procedure for the Amination of 2-[(ω-Bromo Alkyloxy)N-benzyl]4-chlorobenzenesulfanilides

The bromo compound (1.0 eq) was dissolved in neat amine (5.0 eq) (or inDCM (2.0 mL/mmol) if the amine is a solid), and the solution was allowedstir at room temperature under Ar for 1 h. The reaction mixture was thenconcentrated under reduced pressure, re-dissolved in ethyl acetate (25mL/mmol) washed the ethyl acetate solution with saturated bicarbonatesolution and water, dried with MgSO₄, filtered and concentrated underreduced pressure to give the desired product, as the free base, in nearquantitative yield. The free base was converted into the correspondingHCl salt as described elsewhere. The HCl salt was purified by passingthrough a short plug of SiO₂ (10% methanol/DCM) to yield the desiredproduct in >90% yield.

The compounds described in Examples 285-320 were prepared according tothe scheme described in the previous example.

EXAMPLE 285N-[2-(3-bromopropoxy)benzyl]-4-chloro-N-phenylbenzenesulfonamide

R_(f)=0.35 (20% ethyl acetate/hexanes) ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.55-7.47 (m, 2H), 7.19-7.17 (m, 4H), 7.27-7.14 (m, 5H), 6.98 (m, 2H),6.86-6.75 (m, 2H), 4.78 (s, 2H), 3.99 (t, 2H), 3.53 (t, 2H), 2.20 (q,2H).

EXAMPLE 2864-Chloro-N-{2-[(5-chloropentyl)oxy]benzyl}-N-phenylbenzenesulfonamide

R_(f)=0.17 (6% ethyl acetate/hexanes) ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.59-6.70 (m, 13H), 3.82 (t, 2H), 3.56 (t, 2H), 1.83-1.54 (m, 6H).

EXAMPLE 2874-Chloro-N-phenyl-N-{2-[3-(1-pyrrolidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.60 (6:1:DCM:methanol). ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.55-7.47 (m, 4H), 7.19-7.17 (m, 3H), 6.79-6.75 (m, 3H), 6.61 (d, 2H),4.75 (s, 2H), 4.13 (br, 2H), 3.80-3.65 (m, 4H), 3.15 (br, 2H), 2.60 (br,2H), 2.15 (m, 4H).

EXAMPLE 288 Tert-butyl 4-{3-[2-({[(4chlorophenyl)sulfonyl}anilino}methyl)phenoxy]propyl}-1-piperazinecarboxylate

R_(f)=0.13 (5% methanol/DCM) ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.56 (m,2H), 7.45 (m, 2H), 7.32-7.12 (m, 5H), 6.99 (m, 2H), 6.83 (t, 1H), 6.73(d, 1H), 5.30 (s, 2H), 3.89 (t, 2H), 3.44 (t, 4H), 2.50-2.37 (m, 6H),1.87 (q, 2H), 1.47 (s, 9H).

EXAMPLE 2894-Chloro-N-{2-[3-(3,6-dihydro-1(2H)pyridinyl)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.45 (5% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.40 (m,4H), 6.95 (m, 4H), 6.71-6.60 (m, 4H), 6.43 (m, 1H), 5.82 (m, 1H), 5.59(m, 1H), 4.65 (s, 2H), 3.97 (t, 2H), 3.71 (m, 2H), 3.55-3.10 (m, 4H),2.33-1.81 (m, 4H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 158.8, 140.9, 139.9,138.5, 133.4, 131.2, 130.9, 130.8, 130.3, 129.6, 127.1, 124.7, 121.8,121.4, 112.6, 66.3, 55.7, 52.0, 52.0, 51.0, 25.9, 24.1.

EXAMPLE 290N-{2-[3-(4-benzyl-1-piperidinyl)propoxy]benzyl}-4-chloro-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.60 (14% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.54 (m,4H), 7.21-7.06 (m, 9H), 6.82-6.74 (m, 4H), 6.57 (m, 1H), 4.78 (s, 2H),4.07 (m, 2H), 3.55 (m, 4H), 2.99 (m, 2H), 2.58 (m, 2H), 2.27 (m, 2H),1.89-1.51 (m, 5H).

EXAMPLE 291N-{2-[3-(4-benzyl-1-piperidinyl)propoxy]benzyl}4-chloro-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.32 (9% methanol/DCM) ¹H NMR (300 MHz CD₃OD) δ (ppm): 7.40 (m,4H), 6.99 (m, 4H), 6.69-6.44 (m, 5H), 5.80 (s, 2H), 4.66 (s, 2H),4.07-3.96 (m, 6H), 3.62 (m, 2H), 2.11 (m, 2H). ¹³C NMR (75 MHz, CD₃OD) δ(ppm): 161.0, 143.0, 142.0, 140.6, 135.6, 133.4, 133.0, 132.9, 132.4,131.8, 128.7, 126.8, 123.9, 114.7, 68.2, 63.7, 56.9, 54.2, 29.6.

EXAMPLE 292N-{2-[3-(1-azetidinyl)propoxy]benzyl}-4-chloro-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.54 (14% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.61-7.54(m, 4H), 7.16-7.09 (m, 4H), 6.88-6.78 (m, 4H), 6.60 (t, 1H), 4.84 (s,H), 4.25 (t, 4H), 4.08 (m, 2H), 3.67 (m, 2H), 2.52 (m, 2H), 2.10 (m,2H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 158.8, 140.9, 139.9, 138.4, 133.4,131.2, 130.9, 130.77, 130.3, 129.6, 124.6, 121.8, 112.6, 65.8, 56.2,54.1, 52.0, 26.2, 17.6.

EXAMPLE 2934-Chloro-N-phenyl-N-(2-{[5-(1-piperidinyl)pentyl]oxy}benzyl)benzenesulfonamideHydrochloride

R_(f)=0.17 (20% methanol/ethyl acetate) ¹H NMR (300 MHz, CD₃OD) δ (ppm):7.89-7.82 (m, 4H), 7.47-7.36 (m, 4H), 7.27-7.09 (m, 4H), 6.96-6.91 (m,1H), 5.09 (s, 2H), 4.23 (t, 2H), 3.81 (d, 2H), 3.42 (t, 2H), 3.20 (m,2H), 2.25-1.95 (m, 12H).

EXAMPLE 2944-Chloro-N-phenyl-N-[2-[4-(1-piperidinyl)butoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.20 (5% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.38 (m,4H), 6.97 (m, 4H), 6.69 (m, 4H), 6.44 (t, 1H), 4.64 (s, 2H), 3.84 (t,2H), 2.99 (m, 6H), 1.93-1.68 (m, 10H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm):158.5, 140.3, 139.8, 138.3, 132.5, 130.5, 130.4, 130.4, 130.3, 129.8,129.0, 124.5, 121.1, 112.3, 68.1, 58.1, 54.3, 51.3, 27.6, 25.3, 22.7,22.3. ESI calculated for C₂₉H₃₃ClN₂O₃S [MH+] 511; Observed: 511.

EXAMPLE 2954-Chloro-N-{2-[3-(3,4-dihydro-2(1H)-isoquinolinyl)propoxy]benzyl})-N-phenylbenzenesulfonamide

R_(f)=0.50 (50% ethyl acetate/hexanes) ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.59-7.55 (m, 2H), 7.46-7.42 (m, 2H), 7.44 (dd, 1H), 7.22-6.99 (m, 10H),6.84 (t, 1H), 6.74 (t, 1H), 3.92 (t, 2H), 3.62 (s, 2H) 2.91 (t, 2H),2.73 (t, 2H), 2.62 (t, 2H), 1.96 (m, 2H). ¹³C NMR (75 MHz, CDCl₃) δ(ppm): 159.1, 141.7, 141.6, 139.7, 137.2, 136.8, 132.6, 131.6, 131.4,131.3, 131.2, 130.4, 129.1, 128.7, 128.2, 126.4, 122.9, 113.6, 68.6,58.7, 57.4, 53.5, 51.8, 31.7, 29.5. ESI calculated for C₃₁H₃₁ClN₂O₃S[MH+] 547; Observed: 547.

EXAMPLE 2964-Chloro-N-[2-[3-cyclohexylamino)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.20 (14% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.45-7.37(m, 4H), 7.45-7.11 (m, 4H), 7.-7.11 (m, 4H), 6.89 (m, 1H), 5.09 (s, 2H),4.38 (t, 2H), 3.72 (t, 2H), 3.40 (m, 1H), 2.49 (m, 4H), 2.13-1.94 (m,3H), 1.66-1.48 (m, 5H). ¹³C NMR (75 MHz, CD₃OD) δ 158.6, 140.7, 140.1,138.6, 133.0, 131.07, 130.9, 130.9, 130.7, 130.3, 129.6, 124.9, 121.8,112.8, 66.5, 59.1, 51.6, 44.1, 30.9, 28.1, 26.6, 25.9. ESI calculatedfor C₂₈H₃₃ClN₂O₃S [MH+] 513; Observed: 513.

EXAMPLE 2974-Chloro-N-{2-[3-(cyclopropylamino)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.32 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.40-7.32(m, 4H), 6.99-6.89 (m, 5H), 6.76-6.74 (m, 2H), 6.57 (m, 2H), 4.61 (s,2H), 3.71 (t, 2H), 2.66 (t, 2H), 1.99 (m, 1H), 1.71 (m, 2H), 0.30-0.15(m, 4H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 159.0, 141.1, 139.3, 132.6,131.3, 131.2, 131.1, 130.7, 129.8, 125.8, 122.2, 113.2, 68.1, 51.2,48.4, 32.6, 30.8, 6.8. ESI calculated for C₂₅H₂₇ClN₂O₃S [MH+] 471;Observed: 471.

EXAMPLE 2984-Chloro-N-{2-[3-(4-hydroxy-1-piperidinyl)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f) =0.19 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm):7.50-7.43 (m, 4H), 7.07-6.98 (m, 4H), 6.78-6.72 (m, 4H), 6.54-6.49 (m,1H), 4.17 (s, 2H), 3.98 (t, H), 3.81 (m, 1H), 3.39-3.08 (m, 6H),2.20-2.11 (m, 2H), 1.98-1.91 (m, 2H), 1.70 (m, 2H). ¹³C NMR (75 MHz,CD₃OD) δ (ppm): 158.7, 140.8, 140.1, 138.6, 133.2, 131.2, 130.9, 130.9,130.8, 130.3, 129.6, 124.8, 121.8, 112.7, 66.6, 56.3, 51.8, 51.3, 32.6,26.2. ESI calculated for C₂₇H₃₁ClN₂O₄S [MH+] 515; Observed: 515.

EXAMPLE 2994-Chloro-N-phenyl-N-{2-[3-(1-piperazinyl)propoxy]-benzyl}benzenesulfonamideDihydrochloride

R_(f)=0.15 (14% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.80-7.65(m, 5H), 7.33-7.27 (m, 4H), 7.07-6.91 (m, 4H), 6.77 (t, 1H), 5.01 (s,2H), 4.34 (t, 2H), 4.02-3.68 (m, 10H), 2.59 (m, 2H). ¹³C NMR (75 MHz,CD₃OD) δ (ppm): 158.7, 140.8, 139.8, 138.5, 13.3, 133.1, 131.2, 130.9,130.9, 130.8, 130.3, 129.7, 124.7, 121.8, 112.7, 66.1, 56.5, 52.0, 50.3,50.3, 42.4, 25.6. ESI calculated for C₂₁H₃₀ClN₃O₃SCl [MH+] 500;Observed: 500.

EXAMPLE 3004-Chloro-N-(2-{[(2S)-7-methyl-7-azabicyclo[2.2.1]hept-2-yl]methoxy]benzyl)-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.20 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.65-7.59(m, 4H), 7.25-7.16 (m, 41), 7.00-6.93 (m, 4H), 6.73 (m, 1H), 4.88 (q,2H), 4.10 (m, 1H), 3.97 (m, 3H), 2.76 (s, 3H), 2.54 (m, 1H), 2.23-1.78(m, 6H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 158.7, 140.8, 140.3, 138.7,133.0, 131.1, 130.9, 130.8, 130.7, 1303, 129.6, 125.2, 122.0, 113.2,70.5, 68.1, 66.1, 51.7, 43.3, 34.4, 33.8, 3.1, 25.8. ESI calculated forC₂₇N₂O₃SClH₂₉ [MH+] 497; Observed: 497.

EXAMPLE 301N-phenyl-N-{2-[4-(1-piperidinyl)butyl]benzyl}benzenesulfonamide

R_(f)=0.33 (5% methanol/DCM) ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.67-7.62(m, 2H), 7.55-7.50 (m, 2H), 7.21-7.11 (m, 5H), 6.94-6.83 (m, 4H), 4.75(s, 2H), 2.99-2.80 (m; 8H), 2.05-1.62 (m, 10H). ¹³C NMR (75 MHz, CDCl₃)δ (ppm): 141.5, 138.5, 137.9, 133.4, 132.6, 131.4, 130.0, 129.4, 129.2,129.2, 128.7, 128.5, 128.1, 126.2, 57.9, 53.7, 53.0, 31.9, 29.1, 24.5,23.5, 22.9.

EXAMPLE 3024-Chloro-N-{2-[3-(1H-imidazol-1-yl)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.38 (10% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.53-7.38(m, 5H), 7.04-6.93 (m, 5H), 6.85-6.75 (m, 4H), 6.55 (m, 1H), 6.50 (t,1H), 4.70 (s, 2H), 4.18 (t, 2H), 3.72 (t, 2H), 2.06 (m, 2H). ¹³C NMR (75MHz, CD₃OD) δ (ppm): 157.6, 139.6, 139.4, 137.7, 131.9, 129.9, 129.8,129.7, 129.6, 429.2, 128.5, 124.0, 120.6, 111.4, 64.7, 50.5, 44.4, 31.3.ESI calculated for C₂₅H₂₉ClN₃O₃S [MH+] 482; Observed: 482.

EXAMPLE 3034-Chloro-N-{2-[3-(3,5-dimethyl-1-piperidinyl)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.35 (9% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.66-7.58(m, 4H), 7.23-7.14 (m, 4H), 6.99-6.88 (m, 4H), 6.70 (t, 1H), 4.87 (s,2H), 4.09 (t, 2H), 3.44-2.83 (m, 4H), 2.39-1.85 (m, 6H), 1.11-0.77 (m,8H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 158.9, 140.9, 140.3, 138.7, 133.2,131.2, 131.1, 131.02, 130.9, 130.4, 129.7, 125.0, 121.9, 112.8, 67.0,66.9, 60.8, 57.5, 56.8, 51.7, 41.7, 38.5, 31.3, 26.4, 26.3, 19.7, 19.3.

EXAMPLE 3044-Chloro-N-{2-[3-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)propoxy]benzyl}-N-phenylbenzenesulfonamide

R_(f)=0.38 (9% methanol/DCM) ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.58-7.55(m, 2H), 7.4& 7.36 (m, 3H), 7.23-7.11 (m, 4H), 7.00 (dd, 2H), 6.85 (t,1H), 6.72 (d, 1H), 4.79 (s, 2H), 3.83 (t, 2H), 2.52-2.44 (m, 6H),1.90-1.74 (m, 6H). ¹³C NMR (75 MHz, CDCl₃) δ (ppm): 156.8, 139.6, 139.4,137.5, 130.4, 129.5, 129.50, 129.2, 128.2, 124.3, 120.8, 111.4, 107.6,66.7, 64.6, 55.2, 51.8, 49.5, 35.2, 27.4.

EXAMPLE 305N-{2-[3-(1-azepanyl)propoxy]benzyl}-4-chloro-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.19 (9% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.68-7.61(m, 4H), 7.25-7.16 (m, 4H), 6.97-6.86 (m, 4H), 6.68 (m, 1H), 4.89 (s,2H), 4.18 (t, 2H), 3.69 (m, 2H), 3.50 (t, H), 2.37 (m, 2H), 2.00 (b,4H), 1.79 (m, 4H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 161.0, 143.0, 142.2,140.7, 135.5, 133.4, 133.1, 133.0, 132.5, 131.9, 126.9, 124.0, 114.8,68.7, 59.3, 58.7, 54.1, 30.2, 28.4, 27.6.

EXAMPLE 3064-Chloro-N-(2-{3-[(2R,6S)-2,6-dimethylpiperidinyl]propoxy}benzyl)-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.23 (9% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.44 (m,4H), 7.06-7.99 (m, 4H), 6.85-6.72 (m, 4H), 6.57 (m, 1H), 4.70 (s, 2H),3.96 (t, 2H), 3.43-3.23 (m, 6H), 2.11-1.51 (m, 8H), 1.29 (d, 6H). ¹³CNMR (75 MHz, CD₃OD) δ (ppm): 158.4, 140.8, 140.3, 138.7, 132.6, 130.9,130.7, 130.4, 129.6, 125.2, 122.1, 113.1, 66.8, 61.2, 51.1, 24.0, 19.2.ESI calculated for C₂₉H₃₅ClN₂O₃S [MH+] 527; Observed: 527.

EXAMPLE 3074-Chloro-N-{2-[3-(4-oxo-1-piperidinyl)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.25 (5% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.76-7.64(m, 4H), 7.33-7.18 (m, 5H), 7.06 (dd, 2H), 6.94 (d, 1H), 6.84 (t, 1H),4.82 (s, 2H), 3.99 (t, 2H), 2.72 (t, 4H), 2.60 (m, 2H), 2.39 (t, 4H),1.87 (m, 2H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 212.0, 159.4, 141.9,141.8, 139.9, 139.2, 131.9, 131.8, 131.7, 131.6, 130.7, 126.6, 123.1,113.8, 68.7, 56.8, 55.9, 52.3, 44.0, 30.0.

EXAMPLE 3084-Chloro-N-phenyl-N-{2-[3-(4-thiomorpholinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.40 (5% methanol/DCM) ¹H NMR (300 MHz, DMSO) δ (ppm): 7.40 (dd,4H), 7.04-6.88 (m, 4H), 6.77 (m, 2H), 6.57 (dt, 3H), 4.51 (s, 2H), 3.63(t, 2H), 2.35-2.25 (m, 10H), 1.51 (m, 2H). ¹³C NMR (75 MHz, CDCl₃) δ(ppm): 156.9, 139.4, 139.4, 137.5, 130.6, 129.4, 129.2, 129.2, 129.2,128.2, 124.18, 120.7, 111.3, 66.3, 56.1, 55.4, 49.7, 28.3, 26.6.

EXAMPLE 3094-Chloro-N-{5-chloro-2-[3-(4-hydroxy-1-piperidinyl)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.18 (10:1; DCM:methanol). ¹H NMR (CD₃OD) δ (ppm): 7.44-7.37 (m,4H), 7.06-7.03 (m, 3H), 6.95 (dd, 1H), 6.76-6.67 (m, 4H), 4.63 (s, 2H),3.88 (t, 2H), 3.71 (br, 1H), 3.21-3.11 (m, 4H), 2.86 (br, 2H), 2.08-1.99(m, 2H), 1.89-1.73 (m, 2H), 1.62 (m, 2H).

EXAMPLE 3104-Chloro-N-{2-[3-(3-hydroxy-1-piperidinyl)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.23 (9% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.66-7.59(m, 4H), 7.23-7.14 (m, 4H), 7.03-6.87 (m, 4H), 6.72 (t, 1H), 4.87 (s,2H), 4.06 (t, 2H), 3.94 (b, 1H), 3.21-3.03 (m, 6H), 2.18-1.56 (m, 6H).¹³C NMR (75 MHz, CD₃OD) δ (ppm): 157.7, 139.8, 139.2, 137.6, 131.9,130.0, 129.9, 129.8, 129.7, 129.2, 128.5, 124.0, 120.7, 111.7, 66.0,65.1, 59.6, 55.9, 53.8, 50.4, 31.4, 25.5, 20.3.

EXAMPLE 3114-Chloro-N-(2-{3-[4-(hydroxymethyl)-1-piperidinyl]propoxy}benzyl)-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.20 (9% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.41-7.34(m, 4H), 6.99-6.90 (m, 4H), 6.71-6.63 (m, 4H), 6.43 (m, 1H), 4.63 (s,2H), 3.90 (t, 2H), 3.47-3.24 (m, 6H), 2.82 (m, 2H), 2.09 (m, 2H),1.81-1.33 (m, 5H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 158.6, 140.7, 139.8,138.3, 133.1, 131.0, 130.7, 130.56, 130.1, 129.4, 124.5, 121.6, 112.4,66.8, 66.3, 56.2, 54.1, 51.6, 37.9, 27.7, 26.0.

EXAMPLE 3124-Chloro-N-{2-[3-(4-hydroxy-4-methyl-1-piperidinyl)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.3 (1:10; methanol:DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm):7.52-7.45 (m, 4H), 7.09-7.01 (m, 4H), 6.91-6.73 (m, 4H), 6.53 (m, 1H),4.74 (s, 2H), 4.01 (s, 2H), 3.46-3.22 (m, 6H), 2.19 (m, 2M), 1.84-1.68(m, 4H), 1.18 (s, 3H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 159.4, 141.4,140.6, 139.2, 133.9, 131.8, 131.5, 131.5, 131.4, 130.9, 130.3, 125.4,122.4, 113.3, 67.1, 66.9, 56.7, 52.5, 51.4, 37.6, 30.7, 26.8.

EXAMPLE 3134-Chloro-N-{2-[3-(1,1-dioxido-4-thiomorpholinyl)propoxy]benzyl}-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.45 (67% ethyl acetate/hexanes) ¹H NMR (300 MHz, DMSO) δ (ppm):7.72-7.60 (m, 4H), 7.30-7.13 (m, 5H), 7.01 (dd, 2H), 6.89 (d, 1H), 6.79(t, 1H), 4.77 (s, 2H), 3.92 (t, 2H), 3.09 (m, 4H), 2.88 (m, 4H), 2.62(t, 2H), 1.78 (m, 2H). ¹³C NMR (75 MHz, CDCl₃) δ (ppm): 155.9, 138.3,138.1, 136.3, 130.0, 128.4, 128.3, 128.3, 128.2, 128.1, 127.2, 122.8,119.5, 110.2, 64.7, 52.6, 52.5, 49.9, 49.1. ESI calculated forC₂₆H₂₉ClN₂S₂O₅ [MH+] 549; Observed: 549.

EXAMPLE 3144-Chloro-N-(2-{3-[4-hydroxy-4-(trifuoromethyl)-1-piperidinyl]propoxy}benzyl)-N-phenylbenzenesulfonamideHydrochloride

R_(f)=0.23 (5% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.4-7.35(m, 4H), 7.01-6.91 (m, 5H), 6.78-6.74 (m, 2H), 6.58-6.52 (m, 2H) 4.63(s, 2H), 3.73 (t, 2H), 2.68 (m, 2H), 2.42 (m, 2H), 2.19 (dt, 2H),1.79-1.53 (m, 6H). ¹³C NMR (75 MHz, CD₃OD) δ (ppm): 160.9, 142.9, 141.1,134.5, 133.1, 133.0, 132.90, 132.8, 132.4, 131.6, 127.6, 123.9, 114.9,73.9, 73.6, 69.9, 58.9, 53.1, 51.5, 32.9, 30.0. ESI calculated forC₂₈H₃₀ClF₃N₂O₄S [MH+] 583; Observed: 583.

EXAMPLE 3154-Chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-pyrrolidinyl)propoxy]benzyl}benzenesulfonamideHydrochloride

R_(f)=0.40 (10:1;DCM:methanol). ¹H NMR (300 MHz, CD₃OD) δ (ppm):7.85-7.74 (m, 4H), 7.31 (dt, 1H), 7.16-6.76 (m, 6H), 4.96 (s, 2H), 4.26(t, 2H), 3.80 (m, 2H), 3.58 (br m, 4H), 2.48-2.39 (m, 2H), 2.57-2.11 (m,4H).

EXAMPLE 3164-Chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1H-imidazol-1-yl)propoxy]-6-methoxybenzyl}benzenesulfonamideHydrochloride

R_(f)=0.5 (93:7; DCM:methanol). ¹H NMR (CDCl₃) δ (ppm): 7.77-7.34 (m,3H), 7.63-7.60 (m, 2H), 722-7.19 (m, 1H), 7.12 (t, 1H), 7.00-6.95 (m,2H), 6.60-6.54 (m, 1H), 6.49-6.46 (m, 1H), 6.37-6.35 (m, 1H), 4.94-4.90(m, 2H), 4.43 (t, 2H), 3.91 (t, 3H), 3.47 (s, 3H), 229 (m, 2H). LC-MSCalculated for C₂₆H₂₄ClF₂N₃O₄S: 547. Observed: 548 (MH⁺).

EXAMPLE 3174-Chloro-N-{2-[3-(diethylamino)propoxy]benzyl}-N-(2,5-difluorophenyl)benzenesulfonamideHydrochloride

R_(f)=0.49 (9% methanol in DCM), ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.71(d, 2H), 7.62 (d, 2H), 7.20 (t, 1H), 7.02-6.98 (m, 2H), 6.90 (d, 1H),6.88 (d, 1H), 6.76 (m, 1H), 6.69 (t, 1H), 4.84 (s, 2H), 4.16 (t, 2H),3.64-3.61 (m, 2H), 3.37-3.31 (m, 4H), 2.34-2.31 (m, 2H), 1.38 (t, 6H).

EXAMPLE 3184-Chloro-N-(2,5-difluorophenyl)-N-{1-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propoxy]benzyl}benzenesulfonamide

R_(f)=0.33 (2:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.85-7.26 (m, 2H), 7.74-7.67 (m, 4H), 7.48 (d, 2H), 7.31 (d, 1H), 7.17(t, 1H), 6.94-6.83 (m, 4H), 6.70 (d, 1H), 4.82 (s, 1H), 3.86-3.81 (m,4H), 2.10-2.01 (m, 2H).

EXAMPLE 3194-Chloro-N-(2,5-difluorophenyl)-N-{2-[3-(2,5-dioxo-1-pyrrolidinyl)propoxy]benzyl}benzenesulfonamide

R_(f)=0.73 (5% methanol in CH₂Cl₂) 3H NMR (300 MHz CDCl₃) δ (ppm):7.70-7.67 (d, 2H), 7.49-7.46 (d, 2H), 7.31-7.15 (m, 2H), 6.94-6.83 (4H),6.72-6.69 (d, 1H), 4.89-4.82 (br, 2H), 3.83-3.79 (t, 2H), 3.68-3.63 (t,2H), 2.77-2.64 (br, 4H), 2.05-1.92 (m, 2H). LC-MS calculated forC₂₆H₂₃ClF₂N₂O₅S [MH⁺] 549; Observed: 549.

EXAMPLE 3204-Chloro-N-(2,5-difluorophenyl)-N-{2-[3-(2,6-dioxo-1-piperidinyl)propoxy]benzyl}benzenesulfonamide

R_(f)=0.43 (1:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.68 (d, 2H), 7.48 (d, 2H), 7.36 (d, 1H), 7.17 (m, 1H), 6.94-6.85 (m,4H), 6.69 (d, 1H), 4.85 (s, 2H), 3.86 (t, 2H), 3.77 (t, 2H), 2.65 (t,4H), 1.98-1.82 (m, 4H). MS calculated for C₂₇H₂₅ClF₂N₂O₅S, [MH+] 563;Observed: 563.

EXAMPLE 3214-Chloro-N-(2,5-difluorophenyl)-N-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)benzenesulfonamideHydrochloride

The general synthetic scheme set forth in SCHEME 321 can also be usedfor the preparation of numerous compounds according to the invention.

To a solution of 2′-hydroxy acetophenone (3.0 g, 22 mmol) under Ar, inanhydrous THF (100 mL) was added triphenylphosphine (8.7 g, mm mmol),3-bromopropanol (3.8 g, 27 mmol) and DEAD (5.2 mL, 33 mmol). Thereaction mixture was stirred at room temperature for 14 h, concentratedunder reduced pressure and the product isolated by SiO₂ chromatography(hexanes/ethyl acetate 7:1) to give 4.0 g of product (yield: 71%). ¹HNMR (300 MHz, CD₃OD) δ (ppm): 7.72 (dd, 1H), 7.46 (dt, 1H), 7.02-6.95(m, 2H), 4.22 (t, 2H), 3.61 (t, 2H), 2.60 (s, 3H), 2.38, (p, 2H).

A solution of 2′(3-bromopropyloxy) acetophenone (3.2 g, 12.5 mmol) inmethanol (50 mL) was cooled to 0° C. under Ar atmosphere. Solid NaBH₄(0.475 g, 12.5 mmol) was added in one portion and the reaction mixturewas stirred at 0° C. for 1 h, diluted with 100 mL of water and theproduct extracted with 3×50 mL of ethyl acetate. The combined organicphase was washed with 100 mL of water, dried with anhydrous MgSO₄,filtered and concentrated under reduced pressure to give 3.1 g ofproduct (y: 97%). ¹H NMR (300 MHz CD₃OD) δ (ppm): 7.38 (dd, 1H), 7.23(dt, 1H), 6.98 (t, 1H), 6.89 (d, 1H), 5.13 (q, 1H), 4.17 (t, 2H), 3.61(t, 2H), 2.36 (p, 2H), 1.50 (d, 3H).

Synthesis of R-Alcohol

To a stirred solution of commercially available (Strem)(R)— methyloxazaborolidine (127 M solution in toluene, 3.9 mL, 4.95 mmol) at roomtemperature under Ar was added a solution BH₃.Me₂S (10.5 M, 5.63 mL,59.1 mmol) over a period of 10 min. The reaction mixture was leftstirred at room temperature for 10 min after which time cooled to −20°C. To this cooled solution was added a solution of the ketone (25 33 g,98.5 mmol) in dry DCM (11 mL) via syringe pump over a period of 4 h. Thereaction mixture was left stirred for another 2 h at −20° C. andcarefully quenched with pre cooled methanol. The solvent was removed byconcentrating under reduced pressure to yield the crude product whichwas subsequently purified by SiO₂ chromatography(ethyl acetate:hexanes,1:10) to yield the chiral product as a colorless oil (24 g, 94%, >98% eeby chiral HPLC). The stereochemistry is assigned S, based on theliterature precedents. ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.72 (dd, 1H),7.46 (dt, 1H), 7.02-6.95 (m, 2H), 4.22 (t, 2H), 3.61 (t, 2H), 2.60 (s,3H), 2.38, (p, 2H).

The procedure was repeated with (S)-methyl oxazaborolidine solution toyield the corresponding (R)-alcohol.

To a stirred solution of the racemic alcohol (0.5 g, 1.9 mmol) in dryTHF (10 mL) under Ar was added triphenylphosphine (0.75 g, 2.85 mmol)followed by the sulfonamide (0.91 g, 2.85 mmol). The reaction mixturewas cooled to 0° C. in an ice bath and DEAD (0.45 mL, 2.85 mmol) wasadded over period of 5 min. The reaction mixture was left to stir atroom temperature for 15 h then concentrated under reduced pressure togive the crude product mixture which was subsequently purified bychromatography over SiO₂ (10:1 hexanes/ethyl acetate) to give 465 mg (y:63%) to afford a pale yellow oil. ¹H NMR (500 MHz CDCl₃) δ(ppm):7.62-7.61 (m, 2H), 7.39-7.36 (m, 2H), 7.20 (t, 1H), 6.93 (br, 1H), 6.86(d overlaps br, 3H), 6.77 (br d, 1H), 6.68 (t, 1H), 6.08 (br, 1H),4.19-4.09 (m, 2H), 3.77 (br, 2H), 2.47-2.35 (m, 2H), 1.56 (overlappingd, 3H).

The R and S alcohols were similarly converted to the S and R bromoalkylsulfonamide derivative respectively.

The racemic bromo alkyl sulfonamide derivative (115 mg, 0.21 mmol) wasdissolved in dry piperidine (2 mL) under Ar and stirred at roomtemperature for 1 h. The reaction mixture was concentrated under reducedpressure, re-dissolved in 20 mL of ethyl acetate, washed with saturatedbicarbonate solution (2×10 mL of), water (2×10 mL), dried with MgSO₄,filtered and concentrated under reduce pressure to give 110 mg ofproduct as colorless oil (free base). The free base was converted to theHCl salt as described before, passed through a short plug of SiO₂ (10%methanol in DCM) to yield 85 mg of product as white solid. (y: 70%) ¹HNMR (500 MHz CDCl₃) δ (ppm): 7.68-7.54 (m, 4H), 7.23, 7.01, 6.81, 6.67(br, 6H), 6.25 (q overlaps br, 2H), 4.32-4.21 (m, 2H), 3.70-3.60 (m,4H), 3.10-3.56 (br, 2H), 2.43-2.40 (m, 2H), 2.01-1.75 (m, 5H), 1.55-1.51(m, 4H). ESI calculated for C₂₈H₃₂ClF₂N₂O₃S [MH+] 549; Observed: 549.The R and S bromoalkylsulfonamides were similarly converted to giveenantiomerically enriched products.

To a stirred solution of imidazole (82 mg, 1.2 mmol) in anhydrous THF(5.0 mL) was added 2.0 M n-BuLi Solution in hexanes (600 μL 1.2 mmol).The reaction mixture was stirred at room temperature for 30 min, and asolution of bromoalkyl sulfonamide derivative (220 mg, 0.34 mmol in 5 mLof THF) was added. The reaction mixture was stirred at room temperaturefor 6 h, then quenched with saturated bicarbonate solution, extractedwith ethyl acetate (2×25 mL), the combined organic layer were washedwith water (2×20 mL), dried with MgSO₄, filtered and concentrated togive 200 mg of crude product which was purified by SiO₂ chromatography(5% methanol in DCM) to yield 188 mg of product. R_(f)=0.62 (9:1DCM/methanol). ¹H NMR (CDCl₃, 300 MHz) δ (ppm): 7.63-6.65 (m, 14H),6.25-6.23 (m, 1H), 4.52-4.32 (m, 2H), 4.08-3.88 (m, 2H), 2.44-2.27 9m,2H), 1.25-1.21 (overlapping d, 3H). ¹³C NMR (75 z) (partial list ofresolved lines) δ (ppm): 159.0, 155.81 139.3, 130.1, 137.4, 129.7,129.4, 128.9, 119.1, 117.6 (d), 117.4 (d), 110.9, 64.1, 52.7, 43.6,30.9, 18.4.LC-MS calculated for C₂₆H₂₄ClF₂N₃O₃S: 532; Observed: 532.

The compounds described in Examples 322-331 were prepared according tothe scheme described in the previous example.

EXAMPLE 3224-Chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(1-piperidinyl)propoxy]phenyl}propyl)benzenesulfonamideHydrochloride

R_(f)=0.38 (10% methanol in DCM), ¹H NMR (300 MHz, CD₃OD) δ (ppm): (t,4H), 7.26-7.03 (m, 3H), 6.81 (br, 1H), 6.67-6.55 (m, 2H), 6.13-6.04 (m,2H), 4.32-4.22 (m, 2H), 3.68-3.35 (m, 4H), 3.06 (br, 2H), 2.39-2.38 (m,2H), 1.99-1.55 (m, 8H), 0.80 (d, 3H). MS calculated for C₂₉H₃₃ClF₂N₂O₃S,[MH⁺]563: Observed: 563.

EXAMPLE 3234-Chloro-N-2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.46 (10% methanol in DCM), ¹H NMR (300 MHz, CDCl₃) δ (ppm): 8.21(s, 1H), 7.73-7.42 (m, 6H), 7.20-6.68 (m, 7H), 6.25 (m, 1H), 4.64 (m,2H), 4.10 (br, 2H), 2.44 (m, 2H), 1.55 (br, 3H).LC-MS calculated forC₂₁H₂₄ClF₂N₃O₃S, [MH⁺] 532; Observed: 532.

EXAMPLE 3244-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-tetraazol-1-yl)propoxy]phenyl}ethyl)benzenesulfonamide

R_(f)=0.57 (19:1; DCM:methanol). ¹H NMR (CDCl₃) δ (ppm): 8.98 (s, 1H),7.67-7.62 (m, 2H), 7.48-7.42 (m, 2H), 7.21-7.19 (m, 1H), 695-6.52 (m,5.5H), 6.35-6.28 (m, 1.5H), 5.29-5.06 (m, 1H), 4.95-4.87 (m, 1H),4.17-3.95 (m, 1H), 2.68-2.50-(m, 2H), 1.54-1.46 (br, 3H). LC-MScalculated for C₂₄H₂₂ClF₂N₅O₃S: 534. Observed: 536 (MNa+).

EXAMPLE 3254-Chloro-N-(5-chloro-2-fluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.15 (5% methanol in DCM), ¹H NMR (300 MHz, CD₃OD) δ (ppm):7.81-6.59 (m, 14H), 6.20 (s, 1H), 4.54-4.29 (m, 2H), 4.08-3.90 (m, 2H),2.39-2.14 (m, 2H), 1.63 (br, 3H)). LC-MS calculated for C₂₆H₂₄Cl₂FN₃O₃S,[MH⁺] 548; Observed: 548.

EXAMPLE 3264-Chloro-N-(2,5-dichlorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.72 (10% methanol in DCM), ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.64(d, 2H), 7.53 (d, 2H), 7.41-6.66 (m, 10H), 6.14 (m, 1H), 4.32 (m, 2H),3.94 (m, 2H), 2.30 (m, 2H), 1.63-1.49 (dd, 3H). LC-MS calculated forC₂₆H₂₄Cl₃N₃O₃S, [MH⁺] 564; Observed: 564.

EXAMPLE 3274-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(4-methyl-1H-pyrazol-1-yl)propoxy]phenyl}ethyl)benzenesulfonamide

R_(f)=0.32 (19:1 DCM:methanol). ¹H NMR (CDCl₃) δ (ppm): 7.65-7.62 (d,2H), 7.53 (s, 0.5H), 7.47 (s, 0.5H), 7.40-7.38 (d, 2H), 7.21-7.16 (t,1H), 6.92-6.67 (m, 5.5H), 6.28-6.23 (m, 1.5H), 4.42-4.25 (m, 2H),4.07-3.89 (m, 2H), 2.45-2.27 (m, 2H), 2.24 (s, 1.5H), 2.22 (s, 1.5H),1.53 (d, 3H), LC-MS calculated for C₂₇H₂₆ClF₂N₃O₃S: 546. Observed:546.2.

EXAMPLE 3284-Chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(1H-1,2,3-triazol-1-yl)propoxy]phenyl}ethyl)benzenesulfonamide

R_(f)=0.32 (3:1; hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.66-7.61 (m, 4H), 7.39-7.35 (m, 2H), 7.19-7.10 (m, 1H), 6.92-6.65(5.5H), 6.15-6.11 (m, 1.5H), 4.89-4.81 (m, 2H), 4.10-4.02 (m, 1H),3.95-3.87 (m, 1H), 2.58-2.47 (m, 2H), 1.57 (d, 3H). LC-MS calculated forC₂₅H₂₃ClF₂N₄O₃S: 533. Observed: 230 (M⁺-303).

EXAMPLE 3294-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(2-methyl-1H-imidazol-1-yl)propoxy]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.31 (19:1; DCM:methanol), ¹H NMR (CD₃OD) δ (ppm): 7.42-7.01 (m,6H), 6.79-6.44 (m, 5.5H), 6.07-6.00 (m, 1.5H), 4.43-4.34 (m, 2H),4.08-3.95 (m, 2H), 2.50 (s, 3H), 2.35-2.24 (m, 214), 1.30 (m, 3H). LC-MScalculated for C₂₇H₂₆ClF₂N₃O₃S: 546. Observed: 546 (M⁺).

EXAMPLE 3304-Chloro-N-(2,5-difluorophenyl)-N-(1-[2-[3-(4H-1,2,4-triazol-4-yl)propoxy]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.28 (19:1; DCM:methanol). ¹H NMR (CD₃OD) δ (ppm): 9.43 (s, 1H),8.66 (s, 1H), 7.68-7.54 (m, 4H), 7.19-6.66 (m, 5.5H), 6.25-6.18 (m,1.5H), 4.85-4.76 (m, 2H), 4.14-4.09 (m, 2H), 2.59-02.54 (m, 2H), 1.54(br, 3H). LC-MS calculated for C₂₅H₂₃ClF₂N₄O₃S: 532. Observed 532 (M⁺).

EXAMPLE 3314-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(2H-tetraazol-2-yl)propoxy]phenyl}ethyl)benzenesulfonamide

R_(f)=0.25 (4:1; hexanes:ethyl acetate), ¹H NMR (CDCl₃) δ (ppm): 8.89(s, 1H), 7.67-7.61 (d, 2H), 7.41-7.33 (d, 2H), 7.13-7.10 (m, 1H),6.93-6.66 (m, 6H), 6.23-6.21 (m, 1H), 5.23-5.09 (m, 2H), 4.19-4.09 (m,1H), 4.00-3.93 (m, 1H), 2.66-2.56 (m, 2H), 1.56 (d, 3H). LC-MScalculated for C₂₄H₂₂ClF₂N₅O₃S: 533; observed 566 (MNa⁺).

EXAMPLE 3324-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)benzenesulfonamide

R_(f)=0.33 (19:1; DCM:methanol). ¹H NMR (CDCl₃) δ (ppm): 7.66-7.63 (m,3H), 7.58-7.50 (m, 2H), 7.39 (m, 2H), 7.18 (m, 1H), 7.08 (m, 2H), 6.84(d, 1H), 6.64 (t, 1H), 6.58 (s, 1H), 6.43-6.34 (m, 2H), 4.51-4.41 (m,2H), 4.15-3.91 (m, 3H), 3.53 (d, 10H), 2.42 (m, 2H), 1.88 (m, 1H), 1.42(d, 3H). LC-MS calculated for C₂₇H₂₇Cl₂N₃O₄S: 565; Observed: 565 (Me).

EXAMPLE 3334-Chloro-N-(2,5-difluorophenyl)-N-[1-(2-hydroxyphenyl)ethyl]benzenesulfonamide

R_(f)=0.30 (6:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.82-7.79 (m, 2H), 7.60-7.50 (m, 2H), 7.33-6.91 (m, 6.5H), 6.33-6.19 (m,0.5H), 5.30 (q, 1H), 1.36-1.25 (br, 3H). LC-MS calculated forC₂₀H₁₆ClF₂NO₃S: 423. Observed 446 (MNa⁺).

EXAMPLE 3344-Chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(2-methoxyphenyl)ethyl]benzenesulfonamide

R_(f)=0.32 (15:1 hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.66-7.63 (m, 2H0, 7.39-7.37 (m, 2H), 7.18-7.15 (m, 1H), 6.96-6.66 (m,5.5H), 5.81 (br, 1.5H), 1.67 (s, 1.5H), 1.57 (s, 1.5H).

EXAMPLE 3354-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(2,5-dioxo-1-pyrrolidinyl)propoxy]phenyl}ethyl)benzenesulfonamide

R_(f)=0.46 (3:1; hexanes:ethyl acetate). ¹H NMR CDCl₃) δ: 7.65-7.63 (d,2H), 7.39-7.36 (d, 2H), 7.20-7.14 (m, 1H), 6.95-6.37 (m, 6H), 6.05 (m,1H), 4.06-3.74 (m, 4H), 2.73 (s, 4H), 2.20-2.12 (p, 2H), 1.56 (d, 3H),LC-MS calculated for C₂₇H₂₅ClF₂N₂O₅S: 563.01. Observed 260 (M⁺-303).

EXAMPLE 3364-Chloro-N-(4-fluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.34 (5% methanol in DCM), ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.60(s, 1H), 7.51 (d, 2H), 7.35 (d, 2H), 7.08-6.94 (m, 2H), 6.89-6.76 (m,3H), 6.54-6.46 (m, 2H), 6.35 (d, 1H), 6.24 (dt, 1H), 6.12 (q, 1H),4.44-4.24 (m, 2H), 4.03-3.97 (m, 1H), 3.86-3.79 (m, 1H), 2.39-2.16 (m,2H), 1.43 (d, 314). LC-MS calculated for C₂₆H₂₅ClFN₃O₃S, [MH⁺]514;Observed: 514.

EXAMPLE 3374-Chloro-N-(2,4-difluorophenyl)-N-((1R)-1-(2-[3-(1H-imidazol-1-yl)propoxy)phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.43 (5% methanol in CH₂Cl₂) ¹H NMR (300 MHz CD₃OD) δ (ppm): 7.88(s, 1H), 7.72-7.69 (m, 2H), 7.51-7.48 (m, 2H), 7.40-7.27 (m, 2H),7.17-7.11 (m, 1H), 7.04 (br, 1H), 7.00-6.94 (m, 1H), 6.84-6.49 (m, 4H).,6.28-6.21 (q, 1H), 4.56-4.37 (m, 2H), 4.01-3.89 (m, 2H), 2.3&2.27 (m,2H), 1.46-1.43 (m, 3H). LC-MS calculated for C₂₆H₂₄ClF₂N₃O₃S [MH+] 532;Observed: 532.

EXAMPLE 3384-Chloro-N-(3-fluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.29 (5% methanol in CH₂Cl₂) ¹H NMR (300 MHz CD₃OD) δ (ppm): 7.80(s, 1H), 7.70-7.65 (m, 2H), 7.56-7.52 (m, 2H), 7.27 (s, 1H), 7.24-7.17(m, 1H), 7.01-6.85 (m, 4H), 6.71-6.66 (m, 4H), 6.36-6.29 (q, 1H),4.64-4.43 (m, 2H), 4.21-4.14 (m, 1H), 4.05-3.98 (m, 1H), 2.58-2.30 (m,2H), 1.68-1.51 (m 3H). LC-MS calculated for C₂₆H₂₅ClFN₃O₃S [α]+] 514;Observed: 514.

EXAMPLE 3394-Chloro-N-(2-fluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.33 (5% methanol in CH₂Cl₂) ¹H NMR (300 MHz CD₃OD) δ (ppm):7.68-6.47 (m, 15H), 6.27-6.08 (q, 1H), 4.43-4.27 (m, 2H), 3.88 (br, 2H),2.27-2.14 (m, 2H), 1.41 (br, 3H). LC-MS calculated for C₂₆H₂₅ClFN₃O₃S[MH+] 514; Observed: 514.

EXAMPLE 3404-Chloro-N-(2,6-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.35 (5% methanol in CH₂Cl₂) ¹H NMR (300 MHz CD₃OD) δ (ppm):7.54-7.25 (m, 6H), 7.08-6.34 (in, 8H), 6.13-5.97 (q, 1H), 4.36-4.23 (m,2H), 3.97-3.78 (br, 2H), 2.20-2.10 (br, 2H), 1.35-1.25 (m, 3H). LC-MScalculated for C₂₆H₂₄ClF₂N₃O₃S [H+] 532; Observed: 532.

EXAMPLE 341S{3-[2-({[(4-chlorophenyl)sulfonyl]anilino}methyl)phenoxy]propyl}ethanethioate

To a stirred solution of N-2-(3-bromopropyloxy)benzyl4-chlorobenzenesulfanilide (200 mg, 0.4 mmol) in DMF (5 mL) was addedthe potassium salt of thio acetic acid (92 mg, 0.81 mmol). The reactionmixture was then warmed to 60° C. After 3 h, the reaction mixture wascooled to room temperature, diluted with ethyl acetate (25 mL), washedwith saturated bicarbonate solution (3×10 mL) and saturated brine (2×10mL), dried with MgSO₄, filtered and concentrated under reduced pressureto isolate a colorless oil which was purified by SiO₂ chromatography(7:1, hexanes:ethyl acetate) to afforded the desired product (130 mg, y:63%). R_(f)=0.25 (20% ethyl acetate/hexanes) ¹H NMR (300 MHz, CDCl₃) δ(ppm): 7.60-7.56 (m, 2H), 7.46-7.42 (m, 2H), 7.36 (dd, 1H), 7.23-7.7.12(dd, 2H), 6.85 (t, 1H), 6.70 (d, 1H), 4.82 (s, 2H), 3.85 (t, 2H), 2.95(t, 2H), 2.33 (s, 3H), 1.92 (q, 2H), ¹³C NMR (75 MHz, CDCl₃) δ (ppm):196.0, 156.7, 139.6, 139.4, 137.5, 130.7, 129.5, 129.3, 129.3, 128.3,124.5, 121.0, 111.3, 66.4, 49.8, 31.1, 29.6, 26.2.

EXAMPLE 3424-Chloro-N-phenyl-N-[2-(3-sulfanylpropoxy)benzyl]benzenesulfonamide

A stirred solution of thio acetate analog prepared above (100 mg, 0.2mmol) at ° C. in ethanol (5 mL) was vigorously degassed for 0.5 h, thena solution of degassed 1.0 N NaOH (0.4 mL, 0.4 mmol) vas added. Thereaction mixture was allowed stir at 0° C. for 1 h warmed to roomtemperature stirred at room temperature for 1 h, then diluted withdegassed ethyl acetate (20 mL), washed with saturated bicarbonatesolution (3×10 mL), 10% aqueous HCl (3×10 mL), dried with MgSO₄,filtered and concentrated under reduced pressure to isolate a whitesolid. The crude material was purified by chromatography on SiO₂ (4:1hexanes:ethyl acetate) to give 40 mg of product (y: 44°%). R_(f)=0.25(20% ethyl acetate/hexanes) ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.58-7.56(m, 2H), 7.47-7.54 (m, 2H), 7.34-7.14 (m, 5H), 6.99 (m, 2H), 6.87-6.73(dt, 2H), 4.78 (s, 2H), 3.92 (t, 2H), 2.63 (q, 2H), 1.96 (q, 2H), 1.35(t, 1H). ¹³C NMR (75 MHz, CDCl₃) δ (ppm): 159.1, 141.9, 141.8, 139.9,133.1, 131.8, 131.8, 131.7, 131.6, 130.6, 126.7, 123.2, 113.7, 68.2,52.2, 35.8, 24.0.

The following compounds were prepared according to the scheme describedin the previous example.

EXAMPLE 343N-(2,5-difluorophenyl)-4-(phenylsulfanyl)-N-{2-[3-(phenylsulfanyl)propoxy]benzyl}benzenesulfonamide

R_(f)=0.54 (4:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.63 (d, 2H), 7.54-7.50 (m, 5H), 7.33-7.26 (m, 6H), 7.18 (t, 5H), 6.97(m, 1H), 6.87-6.79 (m, 2H), 4.70 (s, 2H), 3.94 (t, 2H), 3.08 (t, 2H),1.90-1.86 (m, 2H).

EXAMPLE 3444-Chloro-N-(2,5-difluorophenyl)-N-{2-[3-(phenylsulfanyl)propoxy]benzyl}benzenesulfonamide

R_(f)=0.45 (6:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, DMSO) δ (ppm):7.72 (q, 4H), 7.34-7.18 (m, 8H), 7.00-6.98 (m, 2H), 6.89-6.80 (m, 2H),4.73 (s, 2H), 3.95 (t, 2H), 3.09 (t, 2H), 1.91-1.87 (m, 2H).

EXAMPLE 3454-Chloro-N-(2,5-difluorophenyl)-N-{2-[3-(phenylsulfonyl)propoxy]benzyl}benzenesulfonamide

R_(f)=0.40 (3:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.96 (d, 2H), 7.68-7.54 (m, 5H), 7.47 (d, 2H), 7.19-7.10 (m, 2H),6.93-6.68 (m, 5H), 4.77 (s, 2H), 3.97 (t, 2H), 3.38 (t, 2H), 2.24-2.15(m, 2H).

EXAMPLE 3464-Chloro-N-{2-[3-(cyclohexylsulfanyl)propoxy]benzyl}-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.26 (5% methanol in DCM), ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.66(d, 2H), 7.47 (m, 2H), 7.28-7.15 (m, 1H), 7.00 (d, 1H), 6.90 (m, 2H),6.75 (m, 3H), 4.81 (s, 214), 3.92 (m, 2H), 2.66 (m, 3H), 1.94 (m, 4H),1.75 (m, 2H), 1.60 (m, 2H), 1.28 (m, 4H).

EXAMPLE 3474-Chloro-N-{2-[3-(cyclohexylsulfonyl)propoxy]benzyl}-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.29 (3:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.65 (d, 2H), 7.48 (d, 2H), 7.18 (t, 1H), 7.80 (d, 2H), 6.90 (m, 21H),6.76 (m, 3H), 4.78 (s, 2H), 4.10 (t, 2H), 3.29 (t, 2H), 2.94 (m, 1H),2.35 (m, 2H), 2.22 (d, 2H), 1.90 (m, 2H), 1.72-1.19 (m, 6H). MScalculated for C₂₈H₃₀ClF₂NO₅S₂, [MNa⁺] 620; Observed: 620.

EXAMPLE 3484-Chloro-N-{2-[3-(cyclohexylsulfinyl)propoxy]benzyl}-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.32 (1:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.64 (d, 2H), 7.47 (d, 2H), 7.19 (t, 1H), 7.08 (d, 2H), 6.92-6.87 (m,2H), 6.80-6.76 (m, 3H), 4.79 (s, 2H), 4.16-3.98 (m, 2H), 3.12-3.03 (m,1H), 2.87-2.78 (m, 1H), 2.67-2.60 (m, 1H), 2.34 (m, 2H), 2.14 (d, 1H),1.95-1.69 (m, 3H), 1.57-1.24 (m, 6H). MS calculated for C₂₈H₃₀ClF₂NO₄S₂,[MH+] 582; Observed: 582.

EXAMPLE 3494-Chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-methoxyphenyl)sulfanyl]propoxy}benzyl)benzenesulfonamide

R_(f)=0.44 (6:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.67-7.64 (m, 2H), 7.48-7.44 (m, 2H), 7.35-7.32 (m, 2H), 7.31-7.15 (m,3H), 6.91-6.70 (m, 8H), 4.77 (m, 2H), 3.94-3.86 (m, 2H), 3.77 (m, 3H),2.97-2.92 (m, 2H), 1.97-1.88 (m, 2H). MS calculated for C₂₉H₂₆ClF₂NO₄S₂,[MNa⁺]612; Observed: 612.

EXAMPLE 3504-Chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-methoxyphenyl)sulfonyl]propoxy}benzyl)benzenesulfonamide

R_(f)=0.42 (2:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.87 (d, 2H), 7.63 (d, 2H), 7.47 (d, 2H), 7.26-7.11 (m, 2H), 7.00 (d,2H), 6.91-6.75 (m, 4H), 6.69 (d, 1H), 4.74 (s, 2H), 3.96 (t, 2H), 3.86(s, 3H), 3.36-3.31 (m, 2H), 2.22-2.13 (n, 2H). MS calculated forC₂₉H₂₆ClF₂NO₆S₂, [MNa⁺] 644; Observed: 644.

EXAMPLE 3514-Chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-nitrophenyl)sulfanyl]propoxy}benzyl)benzenesulfonamide

R_(f)=0.40 (6:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ Ppm):8.12-8.09 (m, 2H), 7.67-7.63 (m, 2H), 7.49-7.45 (m, 2H), 7.41-7.37 (m,2H), 7.22-7.16 (m, 1H), 7.12-7.09 (m, 1H), 6.91-6.74 (m, 5H), 4.82 (s,2H), 4.05 (t, 2H), 332 (t, 2H), 2.19 (m, 2H).

EXAMPLE 3524-Chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-methoxyphenyl)sulfinyl]propoxy}benzyl)benzenesulfonamide

R_(f)=0.23 (1:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.66-7.54 (m, 4H), 7.49 (d, 2H), 7.20-7.11 (m, 2H), 7.03 (d, 2H),6.94-6.76 (m, 4H), 6.71 (d, 1H), 4.76 (s, 2H), 4.05-3.84 (m, 5H),3.15-2.90 (m, 2H), 2.26-2.00 (m, 2H). MS calculated for C₂₉H₂₆ClF₂NO₅S₂,[MNa⁺] 628; Observed: 628.

EXAMPLE 3534-Chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-nitrophenyl)sulfonyl]propoxy}benzyl)benzenesulfonamide

R_(f)=0.56 (2:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ(ppm):8.40 (d, 2H), 8.25 (d, 2H), 7.59 (d, 2H), 7.48 (d, 2H), 7.19-7.14(t, 1H), 6.89-6.82 (m, 3H), 6.75-6.64 (m, 3H), 4.73 (s, 2H), 4.1 (t,2H), 3.65 (m, 2H), 2.38-2.33 (m, 2H).

EXAMPLE 3544-Chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-nitrophenyl)sulfinyl]propoxy}benzyl)benzenesulfonamide

R_(f)=0.53 (1:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):8.36 (d, 2H), 7.93 (d, 2H), 7.64 (d, 2H), 7.50 (d, 2H), 7.17 (m, 1H),6.91-6.80 (m, 3H), 6.74-6.65 (m, 31H), 4.76 (s, 2H), 4.19-4.02 (m, 2H),0.356-3.47 (n, 1H), 3.23-3.14 (m, 1H), 2.47-2.41 (m, 1H0, 2.17-2.13 (m,1H).

EXAMPLE 3554-Chloro-N-(2-[2-(cyclohexylsulfinyl)ethoxy}benzyl-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.35 (1:2 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.65 (d, 2H), 7.47 (d, 2H), 7.22-7.11 (m, 2H), 6.94-6.80 (m, 5H), 4.84(d, 1H), 4.70 (d, 1H), 4.47-4.27 (m, 2H), 3.19-3.10 (m, 1H), 2.94 (dt,1H), 2.65 (tt, 1H), 2.14 (d, 1H), 2.04-1.88 (m, 3H), 1.73 (m, 1H),1.59-1.25 (m, 4H).

EXAMPLE 3564-Chloro-N-(2-[2-(cyclohexylsulfonyl)ethoxy]benzyl]-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.30 (3:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.65 (d, 2H), 7.47 (d, 2H), 7.26-7.18 (m, 2H), 6.97-6.81 (m, 5H), 4.78(s, 2H), 4.35 (t, 2H), 3.38 (t, 2H), 2.92 (tr, 1H), 2.20 (d, 2H), 2.05(m, 2H), 1.74-1.55 (m, 3H), 1.334-1.20 (m, 3H).

EXAMPLE 3574-Chloro-N-{2-[2-(cyclohexylsulfanyl)ethoxy]benzyl}-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.30 (15:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ(ppm): 7.67 (d, 2H), 7.56 (d, 2H), 7.34 (d, 1H), 7.19 (t, 1H), 6.95-6.86(m, 4H), 6.72 (d, 1H), 4.79 (s, 2H), 3.93 (t, 2H), 2.74 (t, 2H), 2.67(m, 1H), 1.95 (br, 2H), 1.77 (br, 2H), 1.63-1.27 (m, 6H).

EXAMPLE 358

The compounds described in Examples 359-373 were prepared according tothe preparative scheme outlined in the previous example.

EXAMPLE 359N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}nicotinamide

R_(f)=0.43 (19:1; DCM:methanol). ¹H NMR(CDCl₃) δ (ppm): 9.08 (s, 1H),8.68 (m, 1H), 8.19-8.15 (m, 1H), 7.63-7.60 (m, 2H), 7.42-7.47 (m, 4H),6.91-6.66 (m, 6H), 6.20 (q, 1H), 4.22-4.13 (m, 2H), 3.89-3.85 (m, 2H),2.46-2.43 (m, 1H), 2.28-2.19 (m, 1H), 1.44 (d, 3H). LC-MS calculated forC₂₉H₂₆ClF₂N₃O₄S: 586; observed: 586 (M+).

EXAMPLE 360N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methylnicotinamide

R_(f)=0.60 (9:1 CH₂Cl₂:methanol) ¹H NMR (300 MHz CDCl₃) δ (ppm):8.69-8.59 (m, 2H), 7.79-6.11 (m, 13H), 5.80-5.68 (m, 1H), 4.28-3.41 (m,4H), 3.25-2.97 (d, 3H), 2.50-1.98 (br, 2H), 1.66-1.35 (m, 3H). LC-MScalculated for C₃₀H₂₈ClF₂N₃O₄S [MH+] 600; Observed [MH+] 600.

EXAMPLE 361N-{3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N,2,2-trimethylpropanamide

R_(f)=0.28 (3:1; hexanes:ethyl acetate) ¹H NMR (CDCl₃) δ (ppm):7.64-7.61 (m, 2H), 7.39-7.36 (m, 2H), 7.21-7.16 (m, 1H), 6.92-6.65 (m,5.5H), 6.36-6.14 (m, 1.5H), 4.16-3.95 (m, 2H), 3.75-3.57 (m, 2H), 3.18(m, 3H), 2.23-2.05 (m, 2H), 1.57 (d, 3H), 1.29 (s, 9H). LC-MS—calculatedfor C₂₉H₃₃ClF₂N₂O₄S: 579. Observed: 579 (M+).

EXAMPLE 3624-Chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(2-{3-{methyl(methylsulfonyl)amino}propoxy}phenyl)ethyl]benzenesulfonamide

R_(f)=0.25 (2:1 hexanes:ethyl acetate) ¹H NMR (CDCl₃) δ (ppm): 7.65-7.62(d, 2H), 7.42-7.39 (d, 2H), 7.20-7.17 (m, 1H), 6.91-6.34 (m, 6H), 6.19(q, 1H), 4.20-4.06 (m, 2H), 3.64-3.55 (m, 2H), 2.96 (s, 3H), 2.84 (s,3H), 2.25-2.19 (m, 2H), 1.53 (d, 3H). LC-MS calculated forC₂₅H₂₇ClF₂N₂O₅S₂: 573; Observed: 573 (M+).

EXAMPLE 363N-{3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methylnicotinamideHydrochloride

R_(f)=0.56 (19:1; DCM:methanol). ¹H NMR (CD₃OD) δ (ppm): 8.55-8.45 (m,2H), 7.92-6.08 (overlapping m, 12H), 5.45 (q, 1H), 4.08-3.45 (m, 4H),3.10 (s, 1.5H), 2.99 (s, 1.5H), 2.19-2.06 (m, 2H), 1.47 (d, 1.5H), 1.34(d, 1.5H).). LC-MS calculated for C₃₀H₂₈ClF₂N₃O₄S: 600; Observed: 600(M+).

EXAMPLE 364 Tert-butyl6-[{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanllino}methyl)phenoxy]propyl}(methyl)amino-6-oxohexylcarbamate

R_(f)=0.33 (1:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.67-7.64 (d, 2H), 7.48-7.45 (d, 2H), 7.22-7.08 (m, 2H), 6.91-6.73 (m,5H), 4.81 (s, 2H), 4.53 (br, 1H), 3.94-3.86 (m, 2H), 3.58-5.53 (m, 2H),3.12-2.95 (m overlaps d, 5H), 2.30 (t, 2H), 2.04-2.96 (m, 2H), 1.69-1.23(m, 13H).

EXAMPLE 365N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N-methyl-5-(2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide

R_(f)=0.57 (10:1; DCM:methanol). ¹H NMR (CDCl₃) δ (ppm): 7.68-7.65 (d,2H), 7.49-7.46 (m, 2H), 7.22-7.05 (m, 2H), 6.90-6.73 (m, 5H), 5.13 (br,0.5H), 5.06 (br, 0.5H), 4.82-4.81 (d, 2H), 4.63-4.59 (m, 1H), 4.49-4.47(m, 1H), 4.31-4.24 (m, 1H), 3.96-3.87 (m, 2H), 3.59-3.56 (m, 2H),3.17-2.87 (m, 5H), 2.73-2.67 (m, 1H), 2.40-2.32 (m, 2H), 2.08-1.96 (m,2H), 1.70-1.65 (m, 6H).

EXAMPLE 3666-Amino-N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl]-N-methylhexanamideHydrochloride

R_(f)=0.56 (6:1;DCM:methanol). ¹H NMR (CD₃OD) δ (ppm): 7.76-7.52 (m,2H), 7.65-7.61 (m, 2H), 7.22-7.02 (m, 4H), 6.93-6.75 (m, 3H), 4.88 (doverlaps HOD, 2H), 4.01 (t, 1H), 3.93 (t, 1H), 3.71 (t, 1H), 3.63 (t,1H), 3.12 (s, 1.5H), 2.99 (s, 1.5H), 2.93 (t, 1H), 2.86 (t, 1H),2.49-2.42 (m, 2H), 2.12-2.00 (m, 2H), 1.71-1.60 (m, 4H), 1.35-1.32 (m,2H).

EXAMPLE 367N-{3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methylacetamide

R_(f)=0.38 (1:1; hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.65-7.62 (m, 2H), 7.40-7.37 (m, 2H), 7.22-7.16 (m, 1H), 6.91-6.64 (m,5.5H), 6.35-6.16 (m, 15H), 4.12-3.95 (m, 2H), 3.77-3.57 (m, 2H), 3.10(s, 1.5H), 3.0 o (s, 1.5H), 2.17-2.10 (m overlaps two s, 5H), 1.58-1.53(m, 3H). LC-MS calculated for C₂₆H₂₁ClF₂N₂O₄S: 537. Observed 537 (M+).

EXAMPLE 368N-{4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N-methylpropanamide

R_(f)=0.4 (1:1 hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm): 7.63-7.62(d, 2H), 7.39-7.35 (m, 3H), 7.19-7.15 (m, 2H) 6.91-6.64 (m, 5H), 6.06(m, 1H), 4.13-4.00 (m, 2H), 3.49-3.39 (m, 2H), 3.01-2.97 (d, 3H),2.43-2.33 (m, 2H), 1.85-1.83 (m, 4H), 1.57 (d, 3H), 1.17-1.11 (dt, 3H).LC-MS calculated for C₂₈H₃₁ClF₂N₂O₄S: 565; Observed: 565 (M+).

EXAMPLE 369N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N-methylcyclohexanecarboxamide

R_(f)=0.26 (2:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.65 (m, 2H), 7.44 (d, 2H), 7.19-7.11 (m, 2H), 6.90-6.70 (m, 5H), 4.80(d, 2H), 3.90-3.82 (m, 2), 3.58-3.50 (m, 2H), 2.91 (d, 3H), 2.49-2.42(m, 1H), 2.02-1.90 (m, 2H), 1.77-0.83 (m, 11H). MS calculated forC₃₀H₃₃ClFN₂O₄S, [MNa⁺] 613; Observed: 613.

EXAMPLE 370N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N-methylnicotinamide

R_(f)=0.66 (9:1 CH₂Cl₂:methanol) ¹H NMR (300 MHz CDCl₃) δ (ppm):8.65-8.55 (m, 2H), 7.74-7.59 (m, 3H), 7.46-7.43 (d, 2H), 7.35-7.31 (m,1H), 7.19-7.14 (m, 1H), 7.06-6.98 (m, 1H), 6.87-6.61 (m, 5H), 4.80-4.76(br, 1H), 4.45 (br, 1H), 4.01-3.98 (t, 1H), 3.81-3.76 (m, 2H), 3.61-3.57(m, 1H), 3.13-3.04 (d, 3H), 2.18-2.01 (m, 2H). LC-MS calculated forC₂₉H₂₆ClF₂N₃O₄S [MH⁺]586; Observed: 586.

EXAMPLE 3714-Chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(3-pyridinylcarbonyl)-2-piperidinyl]ethoxy}benzyl)benzenesulfonamide

R_(f)=0.50 (1:3 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):8.57 (m, 2H), 7.62-6.89 (m, 13), 5.30-2.88 (m, 15H), 2.30-1.48 (m, 8H).MS calculated for C₃₂H₃₀ClF₂N₃O₄S, [MH⁺] 626; Observed: 626.

EXAMPLE 3724-[2-(1-{[(4-Chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-N-(3-pyridinylmethyl)butanamideHydrochloride

R_(f)=0.53 (5% methanol in CH₂Cl₂) ¹H NMR (300 MHz CD₃OD) δ (ppm): 8.78(s, 1H), 8.69-8.68 (d, 1H), 8.54-8.51 (d, 1H), 7.96-7.92 (m, 1H),7.66-7.63 (d, 2H), 7.52-7.49 (d, 2H), 7.20-6.62 (m, 6H), 6.15-6.09 (q,1H), 4.58 (br, 2H), 4.09-3.99 (m, 2H), 2.75-2.61 (m, 2H), 2.24-2.17 (m,2H), 1.57-1.54 (d, 3H). LC-MS calculated for C₃₀H₂₈ClF₃N₃O₄S [MH⁺] 600;Observed: 600.

EXAMPLE 373 4-benzoyl-N-((1S)-1-{[{3-[2-({[(4-chlorophenyl)sulfonyl]-2,difluoroanilino}methyl)phenoxy]propyl}(methyl)amino]carbonyl}-5-{[5-(2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl]amino}pentyl)benzamide

R_(f)=0.37 (7% Methanol in DCM), ¹H NMR (300 MHz, CDCl₃) δ (ppm):8.15-7.78 (m, 6H), 7.70-7.59 (m, 3H), 7.52-7.45 (m, 4H), 7.15 (t, 1H),7.03 (d, 1H), 6.89-6.72 (in, 5H), 6.443-6.19 (m, 2H), 5.37 (m, 1H), 5.33(s, 2H), 5.12 (m, 1H), 4.86-4.82 (m, 1H), 4.44 (m, 1H), 4.26 (m, 1H),4.01-3.93 (m, 2H), 3.82-3.67 (m, 2H), 3.22-2.65 (m, 9H), 2.17-1.26 (m,24H).

EXAMPLE 374

Numerous compounds according to the invention can be prepared employingthe synthetic scheme set forth in SCHEME 374.

EXAMPLE 375

A suspension of 2-hydroxyphenone (10 mL, 83 mmol), 4-bromobutyric acid(16.6 mL, 116 mmol) and K₂CO₃ (14.4 g, 104 mmol) in acetone was refluxedat 56° C. for 64 h. The reaction mixture was acidified with 1 N HClsolution and the acidic solution was extracted with ethyl acetate (3×50mL). The combined organic phase was washed with H₂O and sat. NaClaqueous solution, dried over MgSO₄. The solution was filtered,concentrated the filtrate to obtain the crude product that purified bySiO₂ chromatography to isolate the desired product 7 (15.5 g, 75%) aswhite solid: R_(f) 0.46 (10:5, hexane-ethyl acetate); ¹H NMR (CDCl₃, 300MHz) δ 7.72 (dd, 1H, J=7.6 Hz, J=1.4 Hz), 7.43 (td, 1H, J=7.6 Hz, J=1.2Hz), 6.96 (m, 2H), 4.13 (m, 4H), 2.62 (s, 3H), 2.54 (t, 2H, J=6.6 Hz),2.18 (m, 2H), 2.26 (t, 3H, J=7.2 Hz).

Compound 7 in the reaction scheme outlined above (3.0 g, 12.0 mmol) wastreated with NaBH₄ (227 mg, 6.0 mmol) in methanol (24 mL) solution inthe presence of CeCl₃.7H₂O (89 mg, 0.24 mmol) at 25° C. for 10 min. Thereaction was quenched with 5% HCl solution. The aqueous phase wasextracted with ethyl acetate. The combined organic phase was washed withH₂O and sat NaCl aqueous solution, then dried over MgSO₄. Concentrationand chromatography afforded compound 8 (3.0 g, 100%) as colorless gum:R_(f) 0.29 (10:5, hexane-ethyl acetate); ¹H NMR (CDCl₃, 300 M}z) δ 7.48(d, 1H, J=7.5 Hz), 7.26 (t, 1H, J=7.6 Hz), 7.05 (t, 1H, J=7.6 Hz), 6.80(d, 1H, J=8.1 Hz), 5.26 (br s, 1H), 4.68 (s, 2H), 4.28 (q, 2H, J=7.2Hz), 4.06 (br s, 1H), 1.59 (d, 3H, J=6.6 Hz), 1.33 (t, 3H, J=7.2 Hz).

EXAMPLE 376Ethyl-4-[2-(1-{[(4-(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butanoate

DEAD (567 μL, 3.6 mmol) was added dropwise to a solution of alcohol 8(666 mg, 3.0 mmol), Triphenylphosphine (944 mg, 3.6 mmol) andsulfonamide (910 mg, 3.0 mmol) in toluene (10 mL) at 25° C. under Ar.The mixture was stirred for 40 h, then diluted with hexane-ethyl acetatesolution (10:3). The generated precipitates were filtered and thefiltrate was concentrated in vacuo. Chromatography afforded the compound(1.16 g, 72%) as colorless gum: R_(f) 0.29 (10:2, hexane-thyl acetate);¹H NMR (CDCl₃, 300 MHz) δ 7.62 (d, 2H, J=8.7 Hz), 7.36 (d, 2H, J=8.7Hz), 7.18 (m, 1H), 6.38-6.95 (m, 6H), 6.01 (m, 1H), 4.17 (q, 2H, J=7.2Hz), 4.04 (m, 1H), 3.98 (m, 1H), 2.61 (t, 2H, J=7.0 Hz), 2.17 (m, 2H),1.58 (d, 3H, J=6.9 Hz), 1.27 (t, 3H, J=7.0 Hz); LCMS 3.86 min, m/z 556(M+H⁺+H₂O, C₂₆H₂₆ClF₂NO₅S requires 538.01).

EXAMPLE 3774-[2-(1-{[(4-Chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butanoicAcid

A solution ofethyl-4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butanoate(1.16 g, 2.2 mmol) in THF (5.2 mL), methanol (1.7 mL) and H₂O (1.7 mL)was treated with LiOH.H₂O (91 mg, 2.2 mmol) at 25° C. for 3 h. Thereaction was then quenched with 1 N HCl solution. The aqueous phase wasextracted with ethyl acetate. The combined organic phase was washed withH₂O and sat. NaCl aqueous solution, then dried over MgSO₄. Concentrationand chromatography afforded the desired product (457 mg, 41%) as whitecrystal: m.p. 141.0-142.0° C.; R_(f) 0.14 (10:10, hexane-ethyl acetate);¹H NMR (CDCl₃, 300 MHz) δ 11.08 (br s, 1H), 7.62 (d, 2H, J=8.4 Hz), 7.35(d, 2H, J=8.7 Hz), 7.16 (t, 1H, J=7.5 Hz), 6.38-6.93 (m, 6H), 6.03 (brs, 1H), 4.06 (m, 2H), 2.70 (t, 2H, J=7.0 Hz), 2.17 (m, 2H), 1.57 (d, 3H,J=6.9 Hz); LCMS 3.05 min, m/z 527.2 (C₂₄H₂₂ClF₂NO₅S requires 509.95).

EXAMPLE 3784-[2-(1-{[(4-Chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-N-methylbutanamide

A mixture of acid4-[2-(1-([(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butanoicacid (107 mg, 0.21 mmol), HOBT (31 mg, 0.23 mmol), EDCI (44 mg, 0.23mmol), Et₃N (88 μL, 0.63 mmol) and CH₃NH₂.HCl (16 mg, 0.23 mmol) inCH₂Cl₂ (1.0 mL) was stirred at 25° C. for 13 h. The mixture was dilutedwith ethyl acetate. The organic solution was washed with H₂O and sat.NaCl solution then dried over MgSO₄. Concentration and chromatographyafforded the amide (107 mg, 97%) as colorless gum: R_(f) 0.32 (10:20,hexane-ethyl acetate); ¹H NMR (CDCl₃, 300 MHz) δ 7.64 (d, 2H, J=6.9 Hz),7.42 (d, 2H, J=7.8 Hz), 7.18 (t, 1H, J=8.7 Hz), 6.36-6.91 (m, 7H), 6.26(q, 1H, 1=6.9 Hz), 4.13 (m, 1H), 4.05 (m, 1H), 2.78 (m, 4H), 2.57 (m,1H), 2.23 (m, 2H), 1.55 (br s, 3H); LCMS m/z 524 (M+H+, C₂₅H₂₅ClF₂N₂O₄Srequires 522.99).

EXAMPLE 3794-[2-(1-{[(4-Chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-N-methoxybutanamide

A mixture of4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butanoicacid (107 mg, 0.21 mmol), HOBT (31 mg, 0.23 mmol), EDCI (44 mg, 0.23mmol), Et₃N (88 μL, 0.63 mmol) and CH₃ONH₂.HCl (19 mg, 0.23 mmol) inCH₂Cl₂ (1.0 mL) was stirred at 25° C. for 13 h. The reaction mixture wasdiluted with ethyl acetate. The organic solution was washed with H₂O andsat. NaCl solution then dried over MgSO₄. Concentration andchromatography afforded the compound (94 mg, 83%) as colorless gum:R_(f) 0.20 (10:10, hexane-ethyl acetate); ¹H NMR (CDCl₃, 300 MHz) δ 9.50(br s, 1H), 7.64 (br s, 2H), 7.43 (br s, 2H), 7.16 (m, 1H), 6.34-6.87(m, 6H), 627 (q, 1H, J=6.9 Hz), 4.14 (m, 1H), 4.06 (m, 1H), 3.74 (s,3H), 2.72 (m, 1H), 2.51 (m, 1H), 2.26 (m, 2H), 1.54 (br s, 3H); LCMS2.95, m/z 562 (M+Na⁺, C₂₅H₂₅ClF₂N₂O₅S requires 538.99).

EXAMPLE 380

Numerous compounds according to the invention can be prepared employingthe general synthetic scheme set forth in SCHEME 380.

A suspension of 2-hydroxyphenone (10 mL, 83 mmol), ethyl iodoacetate(25.0 g, 117 mmol) and K₂CO₃ (12.6 g, 91 mmol) in acetone was refluxedat 60° C. for 28 h. The reaction mixture was then diluted with ether.The ether solution was washed with 1 N NaOH solution, H₂O and sat. NaClaqueous solution, then dried over MgSO₄. Concentration andchromatography afforded compound 9 (8.76 g, 47%) as white solid: R_(f)0.19 (10:2, hexane-ethyl acetate); ¹H NMR (CDCl₃, 300 MHz) δ 7.76 (m,1H), 7.42 (m, 1H), 7.04 (m, 1H), 6.82 (m, 1H), 4.70 (m, 2H), 4.28 (q,2H, J=4.2 Hz), 2.72 (s, 3H), 1.31 (t, 3H, J=7.2 Hz).

Compound 9 in the reaction scheme above (4.6 g, 21 mmol) was treatedwith excess of NaBH₄ in methanol (40 mL) solution in the presence ofCeCl₃.7H₂O (155 mg, 0.40 mmol) at 25° C. for 10 min. The reaction wasthen quenched with 5% HCl solution. The aqueous phase was extracted withethyl acetate. The combined organic phase was washed with H₂O and sat.NaCl aqueous solution, then dried over MgSO₄.

The residue was dissolved in a solution of THF-methanol-H₂O (3:1:1, 20mL) and treated with LiOH.H₂O (1.0 g, 25 mmol) at 25° C. for 3 h. Thereaction mixture was then acidified and extracted with ethyl acetate.The combined organic phase was dried over MgSO₄. Concentration andchromatography afforded compound 10 (3.3 g, 82%) as white solid: R_(f)0.34 (10:1, CH₂Cl₂-methanol); ¹H NMR (CD₃OD, 300 MHz) δ 7.52 (dd, 1H,J=7.6 Hz, J=1.4 Hz), 7.28 (td, 1H, J=7.8 Hz, J=1.5 Hz), 7.06 (t, 1H,J=7.5 Hz), 6.92 (d, 1H, J=8.1 Hz), 5.33 (q, 1H, J=6.6 Hz), 5.03 (br s,2H), 4.79 (s, 2H), 1.51 (d, 3H, J=7.2 Hz).

A mixture of hydroxy acid 10 (980 mg, 5.0 mmol), HOBT (743 mg, 5.5mmol), EDCI (1.05 g, 5.5 mmol), NaHCO₃ (1.26 g, 15.0 mmol) andCH₃NH₂.HCl (371 mg, 5.5 mmol) in DMF (10 mL) was stirred at 25° C. for23 h. The reaction mixture was diluted with ethyl acetate. The organicsolution was washed with H₂O and sat NaCl solution then dried overMgSO₄. Concentration afforded alcohol 11 (664 mg, 64%/o) as colorlesssyrup: R_(f) 0.21 (10:05, CH₂Cl₂-methanol); ¹H NMR (CD₃OD, 300 MHz) δ7.50 (dd, 1H, J=7.6 Hz, J=1.6 Hz), 7.27 (m, 1H), 7.05 (t, 1H, I=7.5 Hz),6.90 (d, 1H, J=8.1 Hz), 5.34 (q, 1H, J=7.2 Hz), 5.01 (br s, 2H), 4.57(d, 2H, J=3.0 Hz), 2.85 (s, 3H), 1.54 (d, 3H, J=7.0 Hz).

EXAMPLE 381[2-(1-{[(4-Chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-N-methylacetamide

DEAD (352 μL, 2.2 mmol) was added dropwise to a solution of alcohol 11(312 mg, 1.5 mmol), Triphenylphosphine (586 mg, 2.2 mmol) andsulfonamide 3 (452 mg, 1.5 mmol) in THF (6 mL) at 25° C. under Ar. Themixture was stirred at 25° C. for 22 h, then concentrated in vacuo.Small amount of crude product was purified by HPLC to afford thecompound (34 mg) as white foam: R_(f) 0.35 (10:10, hexane-ethylacetate); ¹H NMR (CDCl, 300 MHz) δ 7.95 (m, 1H), 7.68 (br s, 2H), 7.44(br s, 2H), 7.26 (br s, 1H), 6.24-6.95 (m, 6H), 6.32 (q, 1H, J=7.2 Hz),4.69 (m, 1H), 4.52 (m, 1H), 2.95 (s, 3H), 1.50 (d, 3H, J=7.2 Hz); LCMS3.46 min, m/z 517.1 (M+Na⁺, C₂₃H₂₁ClF₂N₂O₄S requires 494.94).

A mixture of hydroxy acid 10 (980 mg, 5.0 mmol), HOBT (743 mg, 5.5mmol), EDCI (1.05 g, 5.5 mmol), NaHCO₃ (1.26 g, 15 mmol) and CH₃ONH₂HCl(459 mg, 5.5 mmol) in DMF (20 mL) was stirred at 25° C. for 23 h. Thereaction mixture was diluted with ethyl acetate. The organic solutionwas washed with H₂O and sat. NaCl solution then dried over MgSO₄.Concentration afforded the desired product (340 mg, 30%) as colorlesssyrup: R_(f) 0.19 (10:0.5, CH₂Cl₂-methanol); ¹H NMR (CDCl₃, 300 MHz) δ7.44 (d, 1H, J=7.8 Hz), 7.24 (t, 1H, J=7.2 Hz), 7.00 (t, 1H, J=7.4 Hz),6.88 (d, 1H, J=8.1 Hz), 5.23 (m, 1H), 4.90 (s, 2H), 4.57 (d, 2H, J=2.7Hz), 3.70 (s, 3H), 1.48 (d, 3H, J=6.6 Hz).

EXAMPLE 382[2-(1-{[(4-Chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-N-methoxyacetamide

DEAD (357 μL, 2.3 mmol) was added dropwise to a solution of alcohol 12(340 mg, 1.5 mmol), Triphenylphosphine (595 mg, 2.3 mmol) andsulfonamide 3 (458 mg, 1.5 mmol) in THF (6 mL) at 25° C. under Ar. Themixture was stirred at 25° C. for 22 h, then concentrated in vacuo.Crude product was purified by HPLC to afford the desired product (144mg) as white foam: R_(f) 0.38 (10:10, hexane-ethyl acetate); ¹H NMR(CDCl₃, 300 MHz) δ 10.81 (m, 1H), 7.72 (m, 2H), 7.47 (m, 2H), 7.27 (m,1H), 6.24-6.97 (m, 7H), 4.80 (m, 1H), 4.60 (m, 1H), 3.88 (s, 3H), 1.48(d, 3H, J=6.9 Hz); LCMS 3.19 min, m/z 533 (M+Na⁺, C₂₃H₂₁ClF₂N₂O₅Srequires 510.94).

EXAMPLE 383

Numerous compounds according to the present invention can be preparedemploying the general scheme set forth in SCHEME 383.

EXAMPLE 384

R_(f)=0.25 (3:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ:7.46-7.21 (m, 4H), 6.51-6.40 (dd, 1H), 5.52 (dq, 1H), 2.93-2.89 (m, 1H),1.60-1.33 (dd, 3H).

EXAMPLE 385

R_(f)=0.23 (2:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ:7.66-7.16 (m, 4H), 5.16 (q, 1H), 4.87-4.60 (dd, 2H), 3.13 (b, 2H), 1.59(d, 3H).

EXAMPLE 386

R_(f)=0.25 (15:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ:7.43-7.14 (m, 4H), 5.06 (m, 1H), 4.86-4.56 (dd, 2H), 3.07 (s, 3.07),1.48 (d, 3H), 0.85 (s, 9H), 0.00 (m, 6H).

EXAMPLE 387

R_(f)=0.30 (20:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ:7.64-6.22 (m, 11H), 5.87 (q, 1H), 5.10 (m, 1H), 4.84 (m, 1H), 1.50 (m,3K), 0.97 (s, 91), 0.10 (d, 6H).

EXAMPLE 388

R_(f)=0.25 (3:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ:7.63-7.72 (m, 1H), 6.02 (b, 1H), 5.01-4.85 (m, 2H), 2.53-2.16 (bb, 1H),1.49-1.38 (m, 3H).

EXAMPLE 389

R_(f)=0.25 (3:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ:7.69-6.75 (m, 1H), 5.89 (m, 2H), 5.42-5.30 (m, 1H), 3.09 (s, 3H),1.51-1.39 (m, 3H).

EXAMPLE 3904-Chloro-N-(2,5-difluorophenyl)-N-[2-(1H-tetraazol-1-ylmethyl)benzyl]benzenesulfonamide

R_(f)=0.48 (1:1; ethyl acetate:hexanes). ¹H NMR (CDCl₃) δ μm): 8.96 (s,1H), 7.76-7.74 (d, 2H), 7.60-7.58 (d, 2H), 7.35-7.09 (m, 3H0, 6.99-6.90(m, 3H), 6.75-6.69 (m, 1H), 5.93 (s, 2H), 4.82 (s, 2H). LC-MS calculatedfor C₂₁H₁₆ClF₂N₅O₂S 476; Observed: 476.

EXAMPLE 3914-Chloro-N-(2,5-difluorophenyl)-N-[2-(2H-tetraazol-2-ylmethyl)benzyl]benzenesulfonamide

R_(f)=0.50 (2:1; hexanes:ethyl acetate) δ (ppm): 8.515 (s, 1H),7.76-7.72 (m, 2H), 7.54-7.51 (m, 2H), 7.23-6.69 (m, 7H), 6.08 (s, 2H0,4.93 (s, 2H). LC-MS calculated for C₂₁H16ClF2N5O2S: 476; Observed: 476.

EXAMPLE 3924-Chloro-N-(2,5-difluorophenyl)-N-[2-(1H-1,2,4-triazol-1-ylmethyl)benzyl]benzenesulfonamide

Mp=147-148 (ethyl acetate/hexanes). R_(f)=0.28 (19:1; DCM:methanol). ¹HNMR δ (ppm): 8.26 (s, 1H), 8.08 (s, 1H), 7.71-7.68 (m, 2H), 7.54-7.51(m, 2H), 7.25-6.71 (m, 7H), 5.60 9s, 2H0, 4.80 (s, 2H). LC-MS calculatedfor C₂₂H₁₇ClF₂N₄S: 475. Observed: 475.

EXAMPLE 3934-Chloro-N-(2,5-difluorophenyl)-N-[2-(1H-imidazol-1-ylmethyl)benzyl]benzenesulfonamide

Mp=166-167 (DCM/hexanes). R_(f)=0.31 (191; DCM:methanol). ¹H NMR δ(ppm): 7.65-7.50 (m, 5H), 7.33-7.07 (m, 3H), 6.99-6.87 (m, 4H), δ72-6.71 (m, 1H), 5.40 (s, 2H), 4.69 (s, 21). LC-MS calculated forC₂₃H₁₇ClF₂N₃O₂S: 474. Observed 474.

EXAMPLE 3944-Chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[2-(1H-imidazol-1-ylmethyl)phenylethyl}benzenesulfonamide Hydrochloride

R_(f)=0.50 (10:1 DCM:methanol). ¹H NMR (CD₃OD) δ (ppm): 7.77-7.75 (m,2H), 7.63-7.52 (m, 3H), 7.30-6.80 (8.53H), 6.55 (m, 0.5H), 5.88-5.81 (m,2H), 5.49-5.34 (m, 1H), 1.46-1.26 (m, 3H). LC-MS calculated forC₂₃H₂₀ClF₂NO₂S: 487. Observed 488 (MH⁺).

EXAMPLE 3954-Chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[2-(1H-1,2,4-triazol-1-ylmethyl)phenyl]ethyl}benzenesulfonamide

R_(f)=0.25 (97:3; DCM:methanol). ¹H NMR (CD₃OD) δ (ppm): 8.26 (s, 1H),8.00 (s, 1H), 7.70-6.41 (m, 13H), 6.09-5.91 (m, 2H), 5.44 (d, 1H),1.42-1.25 (dd 3H). LC-MS calculated for C23H19ClF2N4O2S: 488. Observed489 (MH+).

EXAMPLE 396

R_(f)=0.34 (6:1; hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm): 8.53(s, 1H), 7.74-6.59 (m, 13H), 6.29-6.22 (m, 1H), 5.84 (d, 1H), 1.42-1.25(dd, 3H). LC-MS calculated for C₂₂H₁₈ClF₂N₅O₂S 489. Observed 490 (MH+).

EXAMPLE 397

R_(f)=0.25 (2:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):8.34 (s,1H), 7.72-7.69 (m, 2H), 7.53-6.35 (m, 10H), 6.37 (d, 1H), 5.91 (q, 1H),5.74 (d, 1H), 1.40-1.24 (dd, 3H).). LC-MS calculated forC₂₂H₁₈ClF₂N₅O₂S: 489. Observed 490 (MH⁺).

EXAMPLE 398

R_(f)=0.50 (10:1 DCM:methanol). ¹H NMR (CDCl₃) δ (ppm):7.66-6.82 (m,11H), 6.14 (br, 1H), δ 3.30-3.14 (m, 6H), 1.83-1.48 (m, 9H). LC-MScalculated for C₂₆H₂₇ClF₂N₂O₂S: 504. Observed 505 (MH+).

EXAMPLE 399

R_(f)=0.25 (3:1 hexanes:ethyl acetate), ¹H NMR (300 M}, CDCl₃) c:7.18-7.06 (m, 3H), 6.37 (d, 1H), 5.23 (q, 1H), 3.01 (d, 1H), 1.58 (t,3H).

EXAMPLE 400

R_(f)=0.23 (2:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ:7.46-7.41 (m, 1H), 7.08-6.98 (m, 2H), 5.10 (q, 1H), 4.80-4.59 (dd, 2H),3.08 (s, 1H), 3.93 (s, 1H), 1.53 (d, 3H).

EXAMPLE 401

R_(f)=0.25 (15:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ:7.37-7.31 (m, 1H), 6.99-6.82 (m, 2H), 4.97 (q, 1H), 4.79-4.52 (dd, 2H),2.76 (b, 1H), 1.39 (d, 3H), 0.79 (s, 9H), 0.00 (d, 6H).

EXAMPLE 402

R_(f)=0.30 (20:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃)δ:7.63-6.16 (m, 10H), 5.58 (q, 1H), 4.79 (m, 2H), 1.36 (m, 3H), 0.79 (s,9H), −0.06 (d, 6H).

EXAMPLE 403

R_(f)=0.25 (3:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃)7.66-7.27 (m, 4H), 7.03-6.47 (m, 6H), 5.94 (d, 1H), 4.94 (m, 2H),2.56-2.26 (bb, 1H), 1.50-1.40 (m, 3H).

EXAMPLE 404

R_(f)=0.30 (15:1 hexanes:ethyl acetate), ¹H NMR (300 M&, CDCl₃) δ7.72-7.41 (m, 4H), 7.10-6.42 (m, 6H), 5.93 (m, 1H), 5.29-5.10 (m, 1H),4.47-4.39 (m, 1H), 1.48-1.23 (m, 3H).

EXAMPLE 405

R_(f)=0.19 (3:1; hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.66-7.74 (m, 2H), 7.56-7.40 (m, 2H), 7.06-6.37 (m, 6H), 6.44-6.37 (m,1H), 4.49 (d overlaps d, 1H), 3.52 (d, 1H), 3.18-3.03 (m, 8H), 1.44 (d,3H). LC-MS calculated for C₂₅H₂₄ClF₃N₂O₄S₂: 572. Observed 572.

EXAMPLE 406

A solution of n-BuLi in THF (2.5 M, 17.6 mL, 44 mmol) was added dropwisewithin 30 min to a solution of (s)-(−)-2-bromo-α-methylbenzyl alcohol(3.9 g, 19.4 mmol) in THF at −78° C. under Ar. After having been stirredfor 40 min, the generated suspension was warmed to 0° C., and ethyleneoxide ((5 mL, 100 mmol) was added. The mixture was stirred at 0° C. for1 h. The reaction was quenched with 1 N HCl aqueous solution. Theaqueous phase was extracted with ethyl acetate. The combined organicsolution was washed with water and sat. NaCl solution, then dried overNa₂SO₄. Concentration and flush column chromatography afforded the diol(1.4 g, 44%) as colorless liquid: R_(f) 0.16 (10:10, hexanes:ethylacetate); ¹H NMR (CDCl₃, 300 MHz) & 7.50 (m, 1H), 7.25 (m, 2H), 7.17 (m,1H), 5.13 (q, 1H, J=6.6 Hz), 3.90 (m, 1H), 3.76 (m, 1H), 3.00 (m, 1H),2.86 (m, 1H), 2.94 (br s, 1H), 1.52 (d, 3H, J=6.6 Hz).

EXAMPLE 407

A solution of the diol prepared according to the previous example (890mg, 5.4 mmol) in CH₂Cl₂ (21 mL) was treated with TBSCl (848 mg, 5.6mmol) in the presence of imidazole (803 mg, 11.8 mmol) at 25° C. underAr for 40 min. The reaction was quenched with H₂O. The aqueous phase wasextracted with CH₂Cl₂. The combined organic phase was dried over Na₂SO₄.Concentration afforded product (1.5 g, 100%) as colorless liquid: R_(f)0.21 (10:1, hexanes:ethyl acetate); ¹H NMR (CDCl₃, 300 MHz) d: 7.50 (m,1H), 7.27 (m, 2H), 7.22 (m, 1H), 5.18 (m, q, 1H, I=6.3 Hz), 3.94 (m,1H), 3.87 (m, 1H), 3.28 (m, 1H), 3.01 (m, 2H), 1.56 (d, 3H, 3=6.3 Hz),0.85 (s, 9H), 0.00 (s, 6H).

EXAMPLE 408

To a solution of the alcohol prepared according to the previous example(4.4 g, 16 mmol) in toluene (53 mL) at 25° C. under Ar, were addedtriphenylphosphine (5.4 g, 20.5 mmol) and sulfonamide 3 (5.3 g, 17.4mmol). The mixture was cooled to 0° C., and DEAD (3.0 mL, 19 mmol) wasadded dropwise. After the addition, the mixture was stirred at 25° C.for 36 h. Concentration and chromatography afforded product 4 (6.66 g,75%) as colorless syrup: R_(f) 0.39 (10:1, hexanes:ethyl acetate); ¹HNMR (CDCl₃, 300 MHz) δ 7.62 (m, 2H), 7.38 (m, 2H), 7.16 (m, 2),6.29-7.07 (m, 5H), 5.94 (m, 1H), 3.86 (m, 2H), 3.26 (m, 1H), 2.79 (m,1H), 1.53 (m, 3H), 0.88 (s, 9H), 0.02 (s, 3H), 0.00 (s, 3H).

EXAMPLE 409

A solution of product prepared according to the previous example (6.6 g,11.7 mmol) in THF (55 mL) was treated with TBAF solution (1.0 M in THF,12 mL, 12.2 mmol) at 25° C. under Ar for 40 min. The reaction wasquenched with H₂O. The aqueous phase was extracted with ethyl acetateand the combined organic solution was washed with sat. NaCl aqueoussolution, then dried over MgSO₄. Concentration and chromatographyafforded4-chloro-N-(2,5-difluorophenyl)-N-{((1R)-1-[2-(2-hydroxyethyl)phenyl]ethyl}benzenesulfonamide(4.8 g, 92%) as colorless gum: R_(f) 0.28 (10:4, hexanes:ethyl acetate);¹H NMR (CDCl₃, 300 MHz) δ7.62 (m, 2H), 7.43 (m, 2H), 7.19 (m, 2H),6.40-7.00 (m, 5H), 5.99 (m, 1H), 3.95 (t, 2H, 3=6.6 Hz), 3.34 (m, 1H),3.00 (m, 1H), 1.92 (s, 1H), 1.48 (m, 3H); LCMS 3.36 min, m/z 469.0(M+H+H₂O, C₂₂H₂₀ClF₂NO₃S requires 451.91).

EXAMPLE 410

A solution of4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[2-(2-hydroxyethyl)phenyl]ethyl}-benzenesulfonamide(422 mg, 0.94 mmol) in triethylamine (5.0 mL) was treated with MsCl (109μL, 1.4 mmol) at 0° C. under Ar for 3 h. The reaction mixture wasdiluted with ethyl acetate. The organic solution was washed with H₂O andsat. NaCl aqueous solution, then dried over MgSO₄. Concentration invacuo afforded the mesylate (450 mg, 91%) as light yellow syrup: R_(f)0.25 (10:4, hexanes:ethyl acetate).

A solution of4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[2-(2-hydroxyethyl)phenyl]ethyl}-benzenesulfonamide(422 mg, 0.94 mmol) in triethylamine (5.0 mL) was treated with MsCl (109μL, 1.4 mmol) at 0° C. under Ar for 3 h. The reaction mixture wasdiluted with ethyl acetate. The organic solution was washed with H₂O andsat. NaCl aqueous solution, then dried over MgSO₄. Concentration invacuo afforded mesylate (450 mg, 91%) as light yellow syrup: R_(f) 0.25(10:4, hexanes:ethyl acetate).

EXAMPLE 411

Imidazole (82 mg, 1.2 mmol) was added slowly to a suspension of NaH(60%, 58 mg, 1.4 mmol) in DMF (2.0 mL) at 25° C. under Ar. After havingbeen stirred at 25° C. for 20 min, the generated solution was added to asolution of mesylate 5 (420 mg, 0.80 mmol) in THF (6.0 mL). The mixturewas stirred at 25° C. overnight. The reaction was quenched with H₂O andthe aqueous phase was extracted with ethyl acetate. The dried organicsolution was concentrated in vacuo. Chromatography afforded4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(1H-imidazol-1-yl)ethyl]phenyl}ethyl)benzenesulfonamidehydrochloride as colorless syrup (211 mg, 53%) as colorless gum: R_(f)0.31 (10:0.5 CH₂Cl₂-methanol); ¹H NMR (CDCl₃, 300 MHz) δ 7.40-7.66 (m,5H), 6.22-7.30 (m, 9H), 5.62 (m, 1H), 4.42 (m, 1H), 4.18 (m, 1H), 3.61(m, 1H), 3.22 (m, 1H), 1.34 (d, 3H, J=6.3 Hz); LCMS calculated forC₂₁H₂₂ClF₂N₃O₂S 502. Observed: 502.

EXAMPLE 4124-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(1H-imidazol-1-yl)ethyl]phenyl}ethyl)benzenesulfonamideHydrochloride

A solution of HCl in Et₂O (1.0 M, 398 μL, 0.40 mmol) was added dropwiseto a solution of4-chloro-N-(2,5-difluorophenyl)-N-(1R)-1-{2-[2-(1H-imidazol-1-yl}ethyl]phenyl}ethyl)benzenesulfonamide hydrochloride (100 mg, 0.20 mmol) in CH₂Cl₂ (2.0 mL)at 25° C. under Ar. After having been stirred for 30 min, the solventswere removed in vacuo. The residue was purified by chromatography toafforded4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(1H-imidazol-1-yl)ethyl]phenyl)ethyl)benzenesulfonamidehydrochloride (99 mg, 92%) as white solid. m.p. 205.0-206.0° C.; R_(f)0.32 (10:0.5, CH₂Cl₂-methanol); ¹H NMR (CD₃OD, 300 MHz) δ 9.22 (s, 1H),7.76-8.07 (m, 6H), 6.57-7.52 (m, 7H), 6.23 (m, 1H), 4.93 (m, 2H), 3.91(m, 1H), 3.78 (m, 1H), 1.69 (d, 3H, J=6.9 Hz); LCMS 3.04 min, m/z 502.05(M+H⁺−HCl, C₂₅H₂₂ClF₂N₃O₂S.HCl requires 501.98 36.46).

EXAMPLE 4134-Chloro-N-(2,5-difluorophenyl-N-((1R)-1-{2-[2-(1H-1,2,4-triazol-1-yl)ethyl]phenyl}ethyl)Benzenesulfonamide

1,2,4-Triazole (101 mg, 1.5 mmol) was treated with NaH (60%, 70 mg, 1.8mmol) in THF (7.0 mL) and DMF (0.5 mL) at 25° C. under Ar for 30 min.The generated suspension was added slowly to a solution of mesylate 5(0.97 mmol) in THF (3.0 mL) and the mixture was stirred for 48 h. Thereaction was quenched with H₂O and the aqueous phase was extracted withethyl acetate. The dried organic solution was concentrated andchromatography afforded4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(1H-1,2,4-triazol-1-yl)ethyl]phenyl}ethyl)benzenesulfonamide(260 mg, 53%) as white crystal: m.p. 116-118° C.; R_(f) 0.28 (10:10,hexanes:ethyl acetate); ¹H NMR (CDCl₃, 300 MHz) δ 8.01 (br 2H), 7.39-73(m, 4H), 6.32-7.11 (m, 7H), 5.83 (m, 1H), 4.65 (m, 1H), 4.89 (m, 1H),3.29-3.68 (m, 2H), 1.35 (m, 3H); LCMS 3.43 min, m/z 503.05 (M+H,C₂₄H₂₁ClF₂N₄O₂S requires 502.96).

EXAMPLE 4144-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(2-methyl-1H-imidazol-1-yl)ethyl]phenyl}ethyl)benzenesulfonamideHydrochloride

2-Methylimidazole (77 mg, 0.94 mmol) was treated with NaH (60%, 27 mg,1.1 mmol) in DMF (1.0 mL) at 25° C. under Ar for 30 min. The generatedsolution was added slowly to a solution of mesylate 5 (250 mg, 0.47mmol) in THF and the mixture was stirred at 25° C. for 26 h. Thereaction was quenched with H₂O and the aqueous phase was extracted withethyl acetate. The dried organic solution was concentrated in vacuo.Chromatography afforded the desired product (39 mg, 16%) as a colorlessgum: R_(f) 0.28 (10:0.5, CH₂Cl₂-methanol); ¹H NMR (CDCl₃, 300 MHz) δ7.60 (m, 2H), 7.42 (m, 2H), 7.15 (m, 2H), 6.20-6.98 (m, &H), 5.52 (m,1H), 4.30 (m, 1H), 4.06 (m, 1H), 3.69 (m, 1H), 3.12 (m, 1H), 2.10 (m,3H), 1.27 (m, 3H); LCMS 3.07 min, m/z 516.10 (M+H+, C₂₆H₂₄ClF₂N₃O₂Srequires 516.00).

4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(2-methyl-1H-imidazol-1-yl)ethyl]phenyl}ethyl)benzenesulfonamide(39 mg, 0.075 mmol) was dissolved in CH₂Cl₂ (2.0 mL) and treated withHCl—Et₂O solution (1.0 M, 83 μL) at 25° C. for 15 min. Solvents wereremoved in vacuo and chromatography afforded4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-(2-[2-(2-methyl-1H-imidazol-1-yl)ethyl]phenyl}ethyl)benzenesulfonamidehydrochloride (26 mg, 61%) as white solid: m.p. 190.5-192.0° C.; R_(f)0.38 (10:1, CH₂Cl₂-methanol); ¹H NMR (CD₃OD, 300 MHz) δ 7.39-7.67 (m,5H), 7.29 (m, 1H), 6.18-7.12 (m, 7H), 5.67 (q, 1H, J=6.9 Hz), 4.44 (m,1H), 4.35 (m, 1H), 3.59 (m, 1H), 3.25 (m, 1H), 2.27 (m, 3H), 1.31 (d,3H, I=6.6 Hz); LCMS 3.07 min, m/z 516.05 (M+H⁺−HCl, C₂₆H₂₄ClF₂N₃O₂S HClrequires 516.00).

The following compounds were prepared using the preparative schemesdescribed in the previous Examples.

EXAMPLE 4154-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(1H-tetraazol-1-yl)ethyl]phenyl}ethyl)benzenesulfonamide

R_(f) 0.16 (10:5, hexanes:ethyl acetate); ¹H NMR (CDCl₃, 300 MHz) δ 8.75(s, 1H), 7.42-7.74 (m, 4H), 6.30-7.20 (m, 7H), 5.94 (m, 1H), 4.98 (m,1H), 4.75 (m, 1H), 3.56 (m, 2H), 1.40 (d, 3H, J=6.9 Hz); LCMS 3.56 min,m/z 504.05 (M+H, C₂₃H₂₀ClF₂N₅O₂S requires 503.95).

EXAMPLE 4164-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(2H-tetraazol-2-yl)ethyl]phenyl}ethyl)benzenesulfonamide

R_(f) 0.40 (10:4, hexanes:ethyl acetate); ¹H NMR (CDCl₃, 300 MHz) δ:8.55 (s, 1H), 7.63 (m, 2H), 7.41 (m, 2H), 6.45-7.14 (m, 7H), 5.88 (m,10H), 5.01 (m, 2H), 3.80 (m, 1H), 3.52 (m, 1H), 1.45 (m, 3H); LCMS 4.37min, m/z 526.05 (M+Na⁺, C₂₃H₂₀ClF₂N₅O₂S requires 503.95).

EXAMPLE 417

R_(f)=0.25 (15:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) o:7.45-6.61 (m, 1H), 5.78 (q, 1H), 3.65-3.52 (m, 2H), 3.00 (m, 1H),2.66-2.55 (m, 1H), 1.79-1.59 (m, 2H), 1.43-1.30 (m, 3H), 0.84 (d, 9H),0.01 (d, 6H).

EXAMPLE 418

R_(f)=0.23 (3:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ:7.66-7.60 (m, 2H), 7.42-7.40 (m, 2H), 7.19-6.59 (m, 7H), 5.94 (q, 1H),3.83-3.76 (m, 2H), 3.21-3.11 (m, 1H), 2.87-2.77 (m, 1H), 2.01-1.88 (m,2H), 1.72 (t, 1H), 1.53 (m, 3H).

EXAMPLE 419

R_(f)=0.30 (3:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ: 7.65(m, 2H), 7.42 (m, 2H), 7.18-6.29 (m, 7H), 6.93 (m, 1H), 4.36 (m, 2H),3.24 (m, 1H), 3.10 (s, 3H), 2.87 (m, 1H), 2.14 (m, 2H), 1.53 (m, 3H).

EXAMPLE 4204-Chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-piperidinyl)propyl]benzyl}benzenesulfonamide

R_(f)=0.25 (9:1;DCM:methanol). ¹H NMR (CD₃OD)δ(ppm):7.75-7.62 (m, 4H),7.19-6.89 (m, 7H), 4.76 (s, overlaps HOD, 2H), 2.95-2.85 (m, 8H),2.11-1.95 (m, 2H), 1.81-1.75 (m, 4H), 1.65-1.55 (m, 2H). LC-MScalculated for C₂₇H₃₀ClF₂N₂O₂S: 519. Observed 519 (M+).

EXAMPLE 4214-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.34 (19:1;DCM:methanol). ¹H NMR (CD₃OD) δ (ppm):7.74 (s, 1H),7.70-7.57 (m, 4H), 7.24 (s, 1H), 7.22-6.61 (m, 8.5H), 6.3 (br m, 0.5H),5.87 (q, 1H), 4.19 (t, 2H), 3.02-2.81 (m, 2H), 2.21-2.11 (m, 2H),1.51-1.49 (m, 3H). LC-MS calculated for C₂₆H₂₄ClF₂N₃O₂S: 516. Observed516 (M+).

EXAMPLE 4224-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-1,2,4-triazol-1-yl)propyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.29 (19:1;DCM:methanol). ¹H NMR (CDCl₃) δ (ppm): 8.19 (s, 1H),8.00 9s, 1H), 7.67-6.30 (m, 11H), 5.92 (q, 1H), 4.36 (t, 2H), 3.17-3.07(m, 1H), 2.91-2.82 (m, 1H), 2.38-2.22 (m, 2H), 1.49 (br, 3H). LC-MScalculated for C₂₅H₂₃ClF₂N₄O₂S: 517. Observed 517 (M+).

EXAMPLE 4234-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(2H-tetraazol-2-yl)propyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.50 (3:1 hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm): 8.81(Ss, 1H), 7.69-6.24 (m, 11), 5.93 (q, 1H), 4.65 (t, 2H), 3.15-2.85 (m,2H), 2.55-2.25 (m, 2H), 1.31 (d, 3H). LC-MS calculated forC₂₄H₂₂ClF₂N₅O₂S: 518. Observed 215 (M⁺-303).

EXAMPLE 4244-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-tetraazol-1-yl)propyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.20 (2:1 hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm): 9.23 (s,1H), 7.70-0.27 (m, 1H), 5.92 (q, 1H), 4.65 (t, 2H), 3.20-2.90 (m, 2H),2.54-2.33 (m, 2H), 1.46 (d, 3H). LC-MS calculated for C₂₁H₂₂ClF₂N₅O₂S:518. Observed 518 (M+).

EXAMPLE 4254-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.29 (19:1 DCM:methanol). ¹H NMR (CDCl₃) δ (ppm):7.74-6.57 (m,13H0, 6.28-6.19 (m, 1H), 6.01-5.94 (m, 1H), 0004.19-4.03 (m, 2H),3.86-3.75 (m, 1H), 3.42-3.16 (m, 2H), 2.93-2.83 (m, 1H), 2.28-1.98 (m,4H), 1.39 (d, 3H). LC-MS calculated for C₂₇H₂₇Cl₂N₃O₃S: 544.5. Observed:544.5 (M+).

EXAMPLE 4264-Chloro-2-[[(4-chlorophenyl)sulfonyl]((1R)-1-{2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)amino]benzylAcetate

R_(f)=0.26 (19:1 DCM:methanol). ¹H NMR (CDCl₃) δ (ppm): 7.68-6.76 (m,14H), 6.23 (d, 1H), 5.97 (q, 1H), 4.36 (d, 1H), 4.15 (t, 2H), 3.58 (d,1H), 3.18-3.09 (m, 1H), 2.97-2.88 (m, 1H), 2.34-2.21 (m, 2H), 1.89 (s,3H), 1.43 (d, 3H).

EXAMPLE 4274-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1-piperidinyl)propyl]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.68 (9:1 DCM:methanol). ¹H NMR (CD₃OD) δ (ppm): 7.57-7.28 (m,5H), 7.09-6.93 (m, 3H), 6.68-6.10 (m, 3H), 5.74 9q, 1H{), 3.87-2.58 (m,8H), 0.1.98-1.85 (m, 2H), 1.71-1.61 (m, 4H), 1.49-1.16 (m, 5H).). LC-MScalculated for C₂₈H₃₁ClF₂N₂O₂S: 533. Observed: 533 (M+).

EXAMPLE 428

A solution of 9-BBN in THF (0.5 M, 91 mL, 45 mmol) was added dropwise toa solution of allyloxy-tert-butyldimethylsilane (8.7 g, 50 mmol) in THF(25 mL) at 0° C. under Ar. The mixture was stirred at 0° C. for 1 h,then at 60° C. for additional 1 h. the solution was then cooled to 25°C. To the generated solution at 25° C., were added compound 19 (8.85 g,40 mmol), PdCl₂(dppf) (990 mg, 1.2 mmol) and 3 M NaOH aqueous solution(13.5 mL, 40.4 mmol). The mixture was refluxed at 60° C. for 12 h. Thesolution was extracted with CH₂Cl₂ and the combined organic solution waswashed with sat. NH₄Cl solution and sat. NaCl solution, then dried overMgSO₄. Chromatography afforded the desired product (21) (11.4 g, 90%) ascolorless syrup: R_(f) 0.12 (10:1, hexanes:ethyl acetate); ¹H NMR(CDCl₃, 300 MHz) δ 7.41 (m, 1H), 7.69 (m, 2H), 5.09 (m, 1H), 3.58 (m,2H), 2.66 (m, 2H), 2.1] (s, 1H), 1.73 (m, 2H), 1.39 (m, 3H), 0.84 (s,9H), −0.01 (s, 3H), −0.02 (s, 3H).

EXAMPLE 429

R_(f)=0.30 (10:5, hexanes:ethyl acetate); ¹H NMR (CDCl₃, 300 MHz) δ 7.65(m, 2H), 7.42 (d, 2H), 7.00 (m, 2H), 6.91 (m, 1H), 6.33-6.74 (m, 3H),5.92 (q, 1H, J=6.6 Hz), 3.79 (s, 2H), 3.15 (m, 10H), 2.82 (m, 1H), 2.68(s, 1H), 1.92 (m, 2H), 1.51 (m, 3H); LCMS 3.55 min, m/z 501.15 (M+H+H₂O,C₂₃H₂₁ClF₃NO₃S requires 483.94).

EXAMPLE 4304-Chloro-N-(2,5-difluorophenyl)-N-(1-{4-fluoro-2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.44 (10:1;DCM:methanol). ¹H NMR (CD₃OD) δ (ppm):7.93-6.37 (m,13H), 5.89 (m, 1H), 4.16 (t, 2H), 3.10-2.85 (m, 2H), 2.31-2.17 (m, 2H),1.52-1.50 (m, 3H). LC-MS calculated for C₂₆H₂₃ClF₃N₅O²S: 534. Observed534 (M+).

EXAMPLE 4314-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)benzenesulfonamideHydrochloride

R_(f)=0.38 (19:1;DCM:methanol). ¹H NMR (CDCl₃) δ (ppm): 9.64 (s, 0.4H),9.56 (s, 0.6H), 7.71-7.40 (m, 6H), 7.02-6.20 (m, 6H), 5.92 (q, 1H),4.62-4.47 (m, 2H), 3.15-2.95 (m, 2H), 2.57-2.22 (m, 2H), 1.41 (d, 3H).LC-MS calculated for C₂₆H₂₃ClF₃N₃O₂S: 534. Observed 534 (M+).

EXAMPLE 4324-Chloro-N-2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(1H-1,2,4-triazol-1-yl)propyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.38 (1:1 hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm): 8.19 (s,1H), 8.01 (s, 1H), 7.67-7.45 (m, 4H), 6.70-6.28 (m, 6H), 5.87 (q, 1H),4.34 (t, 2H), 3.11-2.98 (m, 1H), 2.91-2.80 (m, 1H), 238-2.22 (m, 2H),1.46 (d, 3H). LC-MS calculated for C₂H₁₂ClF₃N₄O₂S: 535. Observed 535(M+).

EXAMPLE 4334-Chloro-N-(2-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(2H-tetraazol-2-yl)propyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.33 (3:1 hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm): 8.58 (s,1H), 7.66-7.32 (m, 4H0, 7.01-6.31 (m, 6H), 5.84 (q, 1H), 4.83 (dt, 2H),3.17-3.07 (m, 1H), 2.88-2.78 (m, 1H), 2.43 (p, 2H), 1.52 (d, 3H). LC-MScalculated for C₂₄H₂₁ClF₃N₅O₂S: 536. Observed 233 (M⁺-303).

EXAMPLE 4344-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-[4-fluoro-2-[3-(1H-tetraazol-1-yl)propyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.50 (1:1 hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm): 8.79 (s,1H), 7.69-7.46 (m, 4H0, 7.02-6.23 (m, 6H), 5.92-5.84 (m, 1H), 4.66 (t,2H), 2.39 (t, 2H), 2.49-2.31 9m, 2H), 1.43 (d, 3H).). LC-MS calculatedfor C₂₄H₂₁ClF₃N₅O₂S: 536. Observed 233. (M⁺-303).

EXAMPLE 435

R_(f) =0.42 (19:1 DCM:methanol). ¹H NMR (CDCl₃) δ (ppm): 7.62 (m, 2H),7.47-7.37 (m, 2H), 7.00-6.50 (m, 6H), 5.90 (q, 1H), 3.08-2.98 (m, 1H),2.70-2.60 (m, 1H), 2.53-2.38 (m, 6H), 1.92-1.82 (m, 2H), 1.70-1.63 (m,4H), 1.51 (d, 3H0, 1.50-1.44 (m, 2H). LC-MS calculated forC₂₈H₃₀ClF₃N₂O₂S: 551. Observed 551 (M+).

EXAMPLE 4364-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(4-methyl-1-piperazinyl)propyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.4 (9:1 DCM:methanol). ¹H NMR (CDCl₃) δ (ppm): 7.76-7.51 9m, 2H),7.42-7.37 (m, 2H), 7.02-6.55 (m, 6H), 5.87 (q, 1H), 3.10-3.00 9m, 1H),2.67-2.28 (m, 12H), 1.87-1.75 (m, 2H), 1.58-1.45 (m, 3H). LC-MScalculated for C₂₉H₃₁ClF₂N₃O₂S: 566. Observed 566 (M+).

EXAMPLE 4374-Chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(4-fluoro-2-{3-[2-(trifluoroethyl)-1H-imidazol-1-yl]propyl]phenyl)ethyl]benzenesulfonamide

R_(f)=0.32 (5:2; hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.74-7.40 (m, 6H), 7.01-6.23 (m, 6H), 5.87 (q, 1H), 4.19 (t, 2H),3.01-2.96 (m, 2H), 2.32-2.16 (m, 2H), 1.44 (d, 3H). LC-MS calculated forC₂₇H₂₂ClF₆N₃O₂S: 602. Observed: 602 (M+).

EXAMPLE 438

Numerous compounds according to the invention can be prepared employingthe general scheme set forth in SCHEME 438.

Using the preparative scheme outlined in Example 438, the compounds ofExamples 439-448 were prepared.

EXAMPLE 4394-Chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(4-fluoro-2-{4-[(methylamino)sulfonyl]butyl}phenyl)ethyl]benzenesulfonamide

R_(f)=0.19 (2:1; hexanes:ethyl acetate). ¹H NMR (300 MHz CDCl₃) δ:7.70-7.45 (m, 4H), 7.01-6.32 (m, 6H), 5.89 (q, 1H), 4.95 (m, 2H),322-3.07 (m, 3H), 2.81-2.80 (m overlaps d, 4H), 2.03-1.84 (m, 4H), 1.49(br, 3H). LC-MS calculated for C₂₅H₂₆ClF₃N₂O₄S₂ [M+] 575 Observed 272(M⁺-303).

EXAMPLE 4404-Chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(2-{4-[(ethylamino)sulfonyl]butyl}-4-fluorophenyl)ethyl]benzenesulfonamide

R_(f)=0.23 (3:1; hexanes:ethyl acetate). ¹H NMR (300 MHz CDCl₃) δ:7.70-7.42 9m, 4H), 7.01-6.29 (m, 6H), 5.88 (q, 1H), 4.61 (t, 1H),3.31-3.07 (m, 5H), 2.86-2.72 (m, 1H), 2.03-1.78 (m, 4H), 1.48 (r, 3H),1.21 (t, 3H). LC-MS calculated for C₂₅H₂₈ClF₃N₂O₄S₂ [M+] 589; Observed:286 (M⁺-303).

EXAMPLE 4414-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-(4-thiomorpholinylsulfonyl)butyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.41 (3:1; hexanes:ethyl acetate). ¹H NMR (300 MHz CDCl₃) δ:7.70-7.40 (m, 4H), 7.01-6.28 (m, 6H), 5.88 (q, 1H), 3.65-0.660 (m, 4H),3.17-3.05 (m, 3H0, 2.83-2.69 (m, 5H), 2.10-1.81 (m, 4H), 1.50 (br d,3H). LC-MS calculated for C₂₆H₃₀ClF₃N₂O₄S₃ [M+] 647.2; Observed: 647.

EXAMPLE 4424-Chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(2-{4[(1,1-dioxido-4-thiomorpholinyl)sulfonyl]butyl}-4-fluorophenyl)ethyl]benzenesulfonamide

R_(f)=0.32 (2:1; hexanes:ethyl acetate). ¹H NMR (300 MHz CDCl₃) δ:7.70-7.38 (m, 4H), 6.90-6.31 (m, 6H), 6.00 (m, 1H), 4.10-3.98 (m, 4H),3.41-2.92 (m, 8H), 2.22-1.93 (m, 4H), 1.58 (d, 3H). LC-MS calculated forC₂₈H₃₀ClF₃N₂O₆S₃ [M+] 679.2; Observed: 376 (M⁺-303).

EXAMPLE 4434-Chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(4-fluoro-2-{3-[(methylamino)sulfonyl]propyl}phenyl)ethyl]benzenesulfonamide

R_(f)=0.18 (3:1 hexanes:ethyl acetate) ¹H NMR (300 MHz CDCl₃) δ:7.71-7.47 (m, 4H), 7.01-6.30 (m, 6H), 5.94-5.91 (br, 1H), 4.73 (br, 1H),3.24-3.22 (m, 3H), 3.05-2.83 (m, 4H), 2.20 (br, 2H), 1.45 (s, 3H). LC-MScalculated for C₂₄H₂₄ClF₃N₂O₄S₂ [M+] 561; Observed: 258 (M⁺-303).

EXAMPLE 4444-Chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(2-(3-[(ethylamino)sulfonyl]propyl}-4-fluorophenyl)ethyl]benzenesulfonamide

R_(f)=0.30 (3:1 hexanes:ethyl acetate) ¹H NMR (300 MHz CDCl₃) δ:7.72-7.60 (m, 2H), 7.49-7.42 (m, 2H), 7.05-6.30 (m, 6H), 5.95-5.88 (q,1H), 4.79-4.75 (t, 1H), 3.25-3.17 (m, 5H), 3.00-2.92 (m, 1H), 2.24-2.14(m, 2H), 1.48-1.46 (m, 3H), 1.25-1.18 (m, 3H). LC-MS calculated forC₂₅H₂₆ClF₃N₂O₄S₂ [M+] 575; Observed: 272 (M-303).

EXAMPLE 4454-Chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(2-{3-[(dimethylamino)sulfonyl]propyl}-4-fluorophenyl)ethyl]benzenesulfonamide

R_(f)=0.26 (3:1 hexanes:ethyl acetate) ¹H NMR (300 MHz CDCl₃) δ (ppm):7.68-7.47 (m, 4H), 7.08-6.30 (m, 6H), 5.89 (br, 1H), 3.14-2.88 (m, 10H),2.22 (m, 2H) 1.48-1.46 (br, 3H). LC-MS calculated for C₂₅H₂₆ClF₃N₂O₄S %[M+] 575; Observed: 575.

EXAMPLE 4464-Chloro-N-[(1R)-1-(2-{3-[(diethylamino)sulfonyl]propyl)}-4-fluorophenyl)ethyl]-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.35 (3:1 hexanes:ethyl acetate) ¹H NMR (300 MHz CDCl₃) δ (ppm):7.69-7.44 (m, 4H), 7.03-6.31 (m, 6H), 5.88-5.86 (q, 1H), 3.37-3.09 (m,8H), 2.20-2.15 (m, 2H), 1.49-1.47 (m, 3H), 1.25-1.1.9 (m, 6H). LC-MScalculated for C₂₇H₃₀ClF₃N₂O₄S₂ [M+] 603; Observed: 603.

EXAMPLE 4474-Chloro-N-(2,5-dichlorophenyl)-N-[(1R)-1-(4-fluoro-2-{4-[(methylamino)sulfonyl]butyl}phenyl)ethyl]benzenesulfonamide

R_(f)=0.27 (2:1 hexanes:ethyl acetate) ¹H NMR (300 MHz CDCl₃) δ (ppm):7.71 (d, 2H), 7.50-7.47 (d, 2H), 7.36-7.15 (m, 2H), 6.91-6.72 (m, 2H),6.56-6.37 (m, 2H), 5.92-5.77 (m, 1H), 4.60-4.48 (m, 1H), 3.24-3.12 (m,3H), 2.84-2.69 (m, 4H), 2.06-1.74 (m, 4H), 1.44-1.37 (m, 3H). LC-MScacld for C₂₅H₂₆Cl₃FN₂O₄S₂ [MH+] 608; Observed: 608.

EXAMPLE 4484-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-(4-fluoro-2-{4-[[(methylamino)sulfonyl]butyl}phenyl)ethyl]benzenesulfonamide

R_(f)=0.22 (2:1 hexanes:ethyl acetate) ¹H NMR (300 MHz CDCl₃) δ (ppm):7.68-7.58 (m, 2H), 7.49-7.41 (m, 2H), 7.25-6.51 (m, 6H), 5.91-5.89 (m,1H), 4.50-4.48 (br, 1H), 3.21-3.01 (m, 3H), 2.84-2.82 (m, 4H), 2.01-1.83(m, 4H), 1.49-1.47 (r, 3H). LC-MS calculated for C₂₅H₂₆Cl₂F₂N₂O₄S₂ [M+]591; Observed: 288 (M⁺-303).

EXAMPLE 4494-Chloro-N-phenyl-N-[2-(3-sulfanylpropoxy)benzyl]benzenesulfonamide

Numerous compounds according to the invention can be prepared employingthe general scheme set forth in SCHEME 449.

To a stirred solution of N-2-(3-bromopropyloxy)benzyl4-chlorobenzenesulfanilide (200 mg, 0.4 mmol) in DMF (5 mL) was addedthe potasium salt of thio acetic acid (92 mg, 0.81 mmol). The reactionmixture was then warmed to 60° C. After 3 h, the reaction mixture wascooled to room temperature, diluted with ethyl acetate (25 mL), washedwith saturated bicarbonate solution (3×10 mL) and saturated brine (2×10mL), dried with MgSO₄, filtered and concentrated under reduced pressureto isolate a colorless oil which was purified by SiO₂ chromatography(7:1, hexanes:ethyl acetate) to afforded the desired product (130 mg, y:63%). R_(f)=0.25 (20% ethyl acetate/exanes) ¹H NMR (300 MHz, CDCl₃) δ(ppm): 7.60-7.56 (m, 2H), 7.46-7.42 (m, 2H), 7.36 (dd, 1H), 7.23-7.7.12(dd, 2H), 6.85 (t, 1H), 6.70 (d, 1H), 4.82 (s, 2H), 3.85 (t, 2H), 2.95(t, 2H), 2.33 (s, 3H), 1.92 (q, 2H), ¹³C NMR (75 MHz, CDCl₃) δ (ppm):196.0, 156.7, 139.6, 139.4, 137.5, 130.7, 129.5, 129.3, 129.3, 128.3,124.5, 121.0, 111.3, 66.4, 49.8, 31.1, 29.6, 26.2.

A stirred solution of thio acetate analog prepared above (100 mg, 0.2mmol) at ° C. in ethanol (5 mL) was vigorously degassed for 0.5 h, thena solution of degassed 1.0 N NaOH (0.4 mL, 0.4 mmol) was added. Thereaction mixture was allowed stir at 0° C. for 1 h, warmed to roomtemperature and stirred at room temperature for 1 h, then diluted withdegassed ethyl acetate (20 mL), washed with saturated bicarbonatesolution (3×10 mL), 10% aqueous HCl (3×10 mL), dried with MgSO₄,filtered and concentrated under reduced pressure to isolate a whitesolid. The crude material was purified by chromatography on SiO₂ (4:1hexanes:ethyl acetate) to give 40 mg of product (y: 44%). R_(f)=0.25(20% ethyl acetate/hexanes) ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.58-7.56(m, 2H), 7.47-7.54 (m, 2H), 7.34-7.14 (m, 5H), 6.99 (m, 2H), 6.87-6.73(dt, 2H), 4.78 (s, 2H), 3.92 (t, 2H), 2.63 (q, 2H), 1.96 (q, 2H), 1.35(t, 1H). ¹³C NMR (75 MHz, CDCl₃) δ (ppm): 159.1, 141.9, 141.8, 139.9,133.1, 131.8, 131.8, 131.7, 131.6, 130.6, 126.7, 123.2, 113.7, 68.2,52.2, 35.8, 24.0.

Using the preparative scheme outlined above, the compounds of Examples450-464 were prepared.

EXAMPLE 450N-(2,5-difluorophenyl)-4-(phenylsulfanyl)-N-{2-[3-(phenylsulfanyl)propoxy]benzyl}benzenesulfonamide

R_(f)=0.54 (4:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.63 (d, 2H), 7.54-7.50 (m, 5H), 7.33-7.26 (r, 6H), 7.18 (t, 5H), 6.97(m, 1H), 6.87-6.79 (m, 2H), 4.70 (s, 2H), 3.94 (t, 2H), 3.08 (t, 2H),1.90-1.86 (m, 2H).

EXAMPLE 4514-Chloro-N-(2,5-difluorophenyl)-N-{2-[3-(phenylsulfanyl)propoxy]benzyl}benzenesulfonamide

R_(f)=0.45 (6:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, DMSO) δ (ppm):7.72 (q, 4H), 7.34-7.18 (m, 8H), 7.00-6.98 (m, 2H), 6.89-6.80 (m, 2H),4.73 (s, 2H), 3.95 (t, 2H), 3.09 (t, 2H), 1.91-1.87 (m, 2H).

EXAMPLE 4524-Chloro-N-(2,5-difluorophenyl)-N-{2-[3-(phenylsulfonyl)propoxy]benzyl}benzenesulfonamide

R_(f)=0.40 (3:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.96 (d, 2H), 7.68-7.54 (m, 5H), 7.47 (d, 2H), 7.19-7.10 (m, 2H),6.93-6.68 (m, 5H), 4.77 (s, 2H), 3.97 (t, 2H), 3.38 (t, 2H), 2.24-2.15(m, 2H).

EXAMPLE 4534-Chloro-N-{2-[3-(cyclohexylsulfanyl)propoxy]benzyl}-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.26 (5% methanol in DCM), ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.66(d, 2H), 7.47 (m, 2H), 7.28-7.15 (m, 1H), 7.00 (d, 1H), 6.90 (m, 2H),6.75 (m, 3H), 4.81 (s, 2H), 3.92 (m, 2H), 2.66 (m, 3H), 1.94 (m, 4H),1.75 (m, 2H), 1.60 (m, 2H), 1.28 (m, 4H).

EXAMPLE 4544-Chloro-N-{2-[3-(cyclohexylsulfonyl)propoxy]benzyl}-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.29 (3:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.65 (d, 2H), 7.48 (d, 2H), 7.18 (t, 1H), 7.80 (d, 2H), 6.90 (m, 2H),6.76 (m, 3H), 4.78 (s, 2H), 4.10 (t, 2H), 3.29 (t, 2H), 2.94 (m, 1H),2.35 (m, 2H), 2.22 (d, 2H), 1.90 (m, 2H), 1.72-1.19 (m, 6H). MScalculated for C₂₈H₃₀ClF₂NO₅S₂, [MNa⁺] 620; Observed: 620.

EXAMPLE 4554-Chloro-N-{2-[3-(cyclohexylsulfinyl)propoxy]benzyl}-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.32 (1:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.64 (d, 2H), 7.47 (d, 2H), 7.19 (t, 1H), 7.08 (d, 2H), 6.92-6.87 (m,2H), 6.80-6.76 (m, 3H), 4.79 (s, 2H), 4.16-3.98 (m, 2H), 3.12-3.03 (m,1H), 2.87-2.78 (m, 1H), 2.17-2.60 (m, 1H), 2.34 (m, 2H), 2.14 (d, 1H),1.95-1.69 (m, 3H), 1.57-1.24 (m, 6H). MS calculated for C₂₈H₃₀ClF₂NO₄S₂,[MH] 5682; Observed: 682.

EXAMPLE 456N-(4-bromophenyl)-4-chloro-N-{2-[3-(1-piperidinyl)propoxy]benzenesulfonamideHydrochloride

R_(f)=0.44 (6:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.67-7.64 (m, 2H), 7.48-7.44 (m, 2H), 7.35-7.32 (m, 2H), 7.31-7.15 (m,3H), 6.96-6.70 (m, 8H), 4.77 (m, 2H), 3.94-3.86 (m, 2H), 3.77 (m, 3H),2.97-2.92 (m, 2H), 1.97-1.88 (m, 2H). MS calculated for C₂₉H₂₆ClF₂NO₄S₂,[MNa⁺] 612; Observed: 612.

EXAMPLE 4574-Chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-methoxyphenyl)sulfonyl]propoxy}benzyl)benzenesulfonamide

R_(f)=0.42 (2:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.87 (d, 2H), 7.63 (d, 2H), 7.47 (d, 2H), 7.26-7.11 (m, 2H), 7.00 (d,2H), 6.91-6.75 (m, 4H), 6.69 (d, 1H), 4.74 (s, 2H), 3.96 (t, 2H), 3.86(s, 3H), 3.36-3.31 (m, 2H), 2.22-2.13 (m, 2H). MS calculated forC₂₉H₂₆ClF₂NO₆S₂, [MNa⁺]644; Observed: 644.

EXAMPLE 4584-Chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-methoxyphenyl)sulfinyl]propoxy}benzyl)benzenesulfonamide

R_(f)=0.23 (1:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.66-7.54 (m, 4H), 7.49 (d, 2H), 7.20-7.11 (m, 2H), 7.03 (d, 2H),6.94-6.76 (m, 4H), 6.71 (d, 10H), 4.76 (s, 2H), 4.05-3.84 (m, 5H),3.15-2.90 (m, 2H), 2.26-2.00 (m, 2H).). MS calculated forC₂₉H₂₆ClF₂NO₅S₂, [a+] 628; Observed: 628.

EXAMPLE 4594-Chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-nitrophenyl)sulfonyl]propoxy}benzyl)benzenesulfonamide

R_(f)=0.56 (2:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ(ppm):8.40 (d, 2H), 8.25 (d, 2H), 7.59 (d, 2H), 7.48 (d, 2H), 7.19-7.14(t, 111, 6.89-6.82 (m, 3H), 6.75-6.64 (m, 3H), 4.73 (s, 2H), 4.1 (t,2H), 3.65 (m, 2H), 2.38-2.33 (m, 2H).

EXAMPLE 4604-Chloro-N-2,5-difluorophenyl)-N-(2-{3-[(4-nitrophenyl)sulfanyl]propoxy}benzyl)benzenesulfonamide

R_(f)=0.40 (6:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (Ppm):8.12-8.09 (m, 2H), 7.67-7.63 (m, 2H), 7.49-7.45 (m, 2H), 7.41-7.37 (m,2H), 7.22-7.16 (m, 1H), 7.12-7.09 (m, 1H), 6.91-6.74 (m, 5H), 4.82 (s,2H), 4.05 (t, 2H), 3.32 (t, 2H), 2.19 (m, 2H).

EXAMPLE 4614-Chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-nitrophenyl)sulfinyl]propoxy}benzyl)benzenesulfonamide

R_(f)=0.53 (1:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):8.36 (d, 2H), 7.93 (d, 2H), 7.64 (d, 2H), 7.50 (d, 2H), 7.17 (m, 1H),6.91-6.80 (m, 3H), 6.74-6.65 (m, 3H), 4.76 (s, 2H), 4.19-4.02 (m, 2H),0.356-3.47 (m, 1H), 3.23-3.14 (m, 1H), 2.47-2.41 (m, 1H0, 2.17-2.13 (m,1H).

EXAMPLE 4624-Chloro-N-{2-[2-(cyclohexylsulfinyl)ethoxy]benzyl)-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.35 (1:2 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.65 (d, 2H), 7.47 (d, 2H), 7.22-7.11 (m, 2H), 6.94-6.80 (m, 5H), 4.84(d, 1H), 4.70 (d, 1H), 4.47-4.27 (m, 2H), 3.19-3.10 (m, 1H), 2.94 (dt,1H), 2.65 (tt, 1H), 2.14 (d, 1H), 2.04-1.88 (m, 31), 1.73 (m, 1H),1.59-1.25 (m, 4H).

EXAMPLE 4634-Chloro-N-{2-[2-(cyclohexylsulfonyl)ethoxy]benzyl}-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.30 (3:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.65 (d, 2H), 7.47 (d, 2H), 7.26-7.18 (m, 2H), 6.97-6.81 (m, 5H), 4.78(s, 2H), 4.35 (t, 2H), 3.38 (t, 2H), 2.92 (tr, 1H), 2.20 (d, 2H), 2.05(m, 2H), 1.74-1.55 (m, 3H), 1.334-1.20 (m, 3H).

EXAMPLE 4644-Chloro-N-{2-[2-cyclohexylsulfanyl)ethoxy]benzyl}-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.30 (15:1 hexanes:ethyl acetate), ¹H NMR (300 MHz, CDCl₃) δ(ppm): 7.67 (d, 2H), 7.56 (d, 2H), 7.34 (d, 1H), 7.19 (t, 1H), 6.95-6.86(m, 4H), 6.72 (d, 1H), 4.79 (s, 2H), 3.93 (t, 2H), 2.74 (t, 2H), 2.67(m, 1H), 1.95 (br, 2H), 1.77 (br, 2H), 1.63-1.27 (m, 6H).

EXAMPLE 4654-Chloro-N-(2,5-difluorophenyl)-N-(1R)-1-{2-[(ethylsulfonyl)methyl]4-fluorophenyl}ethyl)benzenesulfonamide

R_(f)=0.4 (3:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm): 7.75-7.65(m, 2H), 7.55-7.44 (m, 2H), 7.17-6.24 (m, 6H), 6.08 (q, 1H), 5.56(overlapping doublets, 1H), 4.17 (overlapping doubletes, 1H), 3.30-3.209m, 2H), 1.61-1.55 (m, 3H), 1.34 (d, 3H). LC-MS calculated forC₂₃H₂₁ClF₃NO₄S₂ [M+] 532; Observed: 229 (M⁺-303).

EXAMPLE 466 Methyl3-{[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl]sulfonyl}propanoate

R_(f)=0.50 (2:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.81-7.67 (m, 2H), 7.57-7.47 (m, 2H), 7.17-6.27 (m, 6H), 6.15-6.03 (m,1H), 5.62-5.58 (overlapping doublets, 1H), 4.26-4.22 (overlappingdoublets, 1 μl), 3.80 (s, 3H), 3.72-3.51 (m, 2H), 3.12-3.05 (m, 2H),1.39-1.25 (br, 3H). LC-MS cacld for C₂₅H₂₃ClF₃NO₆S₂: 590. Observed: 608(M⁺+H₂O).

EXAMPLE 4673-{[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl]sulfonyl}propanoicAcid

R_(f)=0.55 (6:1;DCM:methanol). ¹H NMR (CD₃OD) δ (ppm):7.83-7.54 (m, 4H),721-6.32 (m, 6H), 6.10-6.07 (m, 1H), 5.49-5.44 (m, 1H), 4.64-4.53 (m,1H), 3.64-3.51 (m, 2H), 3.05-2.93 (m, 2H) 1.38 (d, 3H). LC-MS cacld forC₂₄H₂₁ClF₃NO₆S₂: 576. Observed: 576 (Me).

EXAMPLE 468 Methyl(2R)-2-[(tert-butoxycarbonyl)amino]-3-{[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl]sulfanyl}propanoate

R_(f)=0.47 (3:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.74-7.63 (m, 2H), 7.49-7.39 (m, 2H), 7.05-6.41 (m, 6H), 6.05 (br, 1H),5.53 (br, 1H), 4.68-4.62 (m, 1H), 4.47-4.38 (m, 1H), 3.81-3.76 9m, 4H0,3.07-2.97 (m, 2H), 1.48-1.37 (br overlaps s, 12H). LC-MS cacld forC₃₀H₃₂ClF₃N2O₆S₂: 673. Observed: 573 (M⁺-Boc).

EXAMPLE 469 Methyl(2R)-2-[(tert-butoxycarbonyl)amino]-3-{[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl]sulfonyl}propanoate

R_(f)=0.25 (3:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.80-7.69 (m, 2H), 7.58-7.47 (m, 2H), 7.16-7.01 (m, 2H), 6.89-6.62 (m,3H), 6.31-5.91 (m, 2H), 5.61 (br, 1H), 4.91 (br, 1H), 4.31-4.21 (m, 1H),3.92-3.84 (m overlaps s, 5H), 1.50 (s, 9H), 1.36-1.34 (br, 3H). LC-MScacld for C₃₀H₃₂ClF₃N2O₈S₂: 705. Observed: 605 (M⁺-Boc).

EXAMPLE 470 Methyl2-amino-3-{[2-(1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl]sulfonyl}propanoateHydrochloride

R_(f)=0.50 (2:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.76-7.64 (m, 2H), 7.53-7.43 (m, 2H), 7.24-7.16 (m, 1H), 7.05-6.33 (m,5H), 6.13 (br, 1H), 5.57 9d, 1H), 4.82-4.68 (r, 2H), 3.84-3.0 (broverlaps s, 7H), 137-1.35 (br, 31.1). LC-MS cacld for C₂₅H₂₄ClF₃N₂O₆S₂:604. Observed: 605 (MH⁺).

EXAMPLE 471 Methyl(2S)-2-[(tert-butoxycarbonyl)amino]-3-{[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl]sulfonyl}propanoate

R_(f)=0.25 (2:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.76-7.63 (m, 2H), 7.53-7.41 (m 2H), 7.71-7.00 (m, 3H), 6.87-6.32 (m,3H), 6.11-5.81 (m, 2H), 5.63 (m, 1H), 4.81 {br, 1H), 4.59-4.23 (m, 1H),3.94-3.88 (m, 2H), 3.85 (s, 3H), 1.48 (s, 9H), 1.37-1.35 (br, 3H). LC-MScacld for C₃₀H₃₂ClF₃N₂O₈S₂: 705. Observed: 605 (M⁺-Boc).

EXAMPLE 4724-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-[2-[2-(ethylsulfonyl)ethyl]-4-fluorophenyl}ethyl)benzenesulfonamide

R_(f)=0.28 (3:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.68-7.58 (m, 2H), 7.49-7.48 (m, 2H), 7.05-6.41 (m, 6H), 5.89 (q, 1H),3.54-3.20 (m, 6H), 1.50-1.41 (m, 6H).). LC-MS calculated forC₂₄H₂₃ClF₃NO₄S₂ 546; Observed: 242 (M⁺-303).

EXAMPLE 473 Methyl 3-({2-[2-((1R)-1-{1(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl}sulfanyl)propanoate

R_(f)=0.33 (6:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ μm): 7.67-7.54(m, 2H), 7.44-7.35 (m, 2H), 7.00-6.28 (m, 6H), 5.93-5.81 (m, 1H), 3.68(s, 3H), 3.40-3.28 9m, 1H), 2.99-2.65 (m, 7H), 1.53 (br 3H). LC-MS cacldfor C₂₆H₂₅ClF₃NO₄S₂: 572. Observed: 269 (M⁺-303).

EXAMPLE 474 Methyl3-({2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl}sulfonyl)propanoate

R_(f)=0.50 (2:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.72-7.59 (m, 2H), 7.50-7.40 9m, 2H), 7.08-6.42 (m, 6H), 5.97-5.83 (m,1H), 3.72 (s, 3H), 3.57-3.34 (m, 61), 2.98 (t, 3H), 1.50-1.38 (br, 3H).LC-MS cacld for C₂₆H₂₅ClF₃NO₆S₂: 640. Observed: 621 (M⁺+H₂O).

EXAMPLE 4753-({2-[2-((1R)-1-{[(4-chloro-phenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl}sulfonyl)propanoicAcid

R_(f)=0.48 (10:1;DCM:methanol). ¹H NMR (CD₃OD) δ (ppm): 7.89-7.63 (m,2H), 7.58-7.51 (m, 2H), 7.21-7.00 (m, 3H), 6.89-6.45 (m, 3H), 5.95-5.90(m, 1H), 3.60-3.50 (m, 4H), 3.23-3.22 (m, 2H), 2.91-2.83 (m, 2H),1.55-1.42 (br, 3H). LC-MS cacld for C₂₅H₂₃ClF₃NO₆S₂: 589. Observed: 589(M+).

EXAMPLE 476 Methyl({2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl}sulfinyl)acetate

R_(f)=0.45 (1:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.75-7.58 (m, 2H), 7.50-7.40 (m, 2H), 7.08-6.88 (m, 3H), 6.88-6.42 (m,3H), 5.92-5.87 (r, 1H), 3.98-3.79 (m overlaps s, 5H), 3.59-3.21 (m, 4H),1.49-1.44 (m, 3H). LC-MS cacld for C₂₅H₂₃ClF₃NO₅S₂: 574. Observed: 271(M⁺-303).

EXAMPLE 477 Methyl({2-[2-((1R)-1-[[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl}sulfanyl)acetate

R_(f)=0.40 (6:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.71-7.58 (m, 2H), 7.48-7.39 (m, 2H), 7.01-6.33 (m, 6H), 5.90 (q, 1H),3.78 (s, 3H), 3.47-3.45 (m, 3H), 3.00-2.91 (m, 3H), 1.55-1.47 (br, 3H).LC-MS cacld for C₂₅H₂₃ClF₃NO₄S₂: 558. Observed: 255 (M⁺-303).

EXAMPLE 478 Methyl({2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl}sulfonyl)acetate

R_(f)=0.45 (2:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.71-7.61 (m, 2H), 7.51-7.39 (m, 2H), 7.07-6.37 (m, 6H), 5.95-5.89 (m,1H), 4.39-4.34 (m, 1H), 4.15-4.10 (m, 1H), 3.87 (s, 3H), 3.75-3.61 (m,3H), 3.41-3.31 (m, 1H), 1.51-1.41 (br, 3H). LC-MS cacld forC₂₅H₂₃ClF₃NO₆S₂: 590. Observed: 287 (M⁺-303).

EXAMPLE 479 Methyl({2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl}sulfonyl)acetate

R_(f)=0.30 (10:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.71-7.57 (m, 2H), 7.44-7.37 (m, 2H), 7.00-6.31 (m, 6H), 5.88 (q, 1H),3.21-3.09 (m, 1H), 2.83-2.73 (m, 1H), 2.62 (m, 2H), 2.16 (s, 3H),1.99-1.89 (m, 2H), 1.54 (br, 3H).). LC-MS calculated for C₂₄H₂₃ClF₃NO₂S₂[M+] 514; Observed: 211 (M⁺-303).

EXAMPLE 480N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(methylsulfanyl)propyl]phenyl}ethyl)-4-(methylsulfanyl)benzenesulfonamide

R_(f)=0.39 (5:1;hexanes:ethyl acetate). ¹H NMR (CDCl) δ (ppm):7.64-7.50-(m, 2H), 7.23-7.15 (m, 2H), 7.00-6.84 (m, 3H), 6.69-6.33 (m,3H), 5.88-5.79 (m, 1H), 2.21-3.10 (m, 1H), 2.78-2.72 (m, 1H0, 2.61 9t,2H), 2.49 9s, 3H0, 2.14 (s, 3H), 1.98-1.90 (m, 2H), 1.54-1.50 (br,3H).). LC-MS calculated for C₂₅H₂₆F₃NO₂S₃ [M+] 525; Observed: 548(M+Na).

EXAMPLE 4814-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-}4-fluoro-2-[3-(methylsulfonyl)propyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.19 (2:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.73-7.59 (m, 2H), 7.51-7.41 (m, 2H), 7.05-6.30-(m, 6H), 5.91 (q, 1H),3.24-3.03 (m, 4H), 2.98 (s, 3H), 2.27-2.23 (m, 2H), 1.45 (d, 3H). LC-MScalculated for C₂₄H₂₃ClF₃NO₄S₂ [M+] 546; Observed: 243 (M⁺-303).

EXAMPLE 4824-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(ethylsulfanyl)propyl]-4-fluorophenyl}ethyl)benzenesulfonamide

R_(f)=0.31 (10:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.68-7.54 (m, 2H), 7.44-7.38 (m, 2H), 7.00-6.28 (m, 6H), 5.87 (q, 1H),3.22-3.08 (m, 1H), 2.82-2.53 (m, 5H), 1.98-1.86 (m, 2H), 1.55 (br, 3H),1.30 (t, 3H). LC-MS calculated for C₂₅H₂₅ClF₃NO₂S₂ [M+] 528; Observed:225 (M⁺-303).

EXAMPLE 4834-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-[2-[3-(ethylsulfonyl)propyl]-4-fluorophenyl}ethyl)benzenesulfonamide

R_(f)=0.45 (2:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.71-7.60 (m, 2H), 7.52-7.40 (m, 2H), 7.01-6.31 (m, 6H), 5.90 (q, 1H),3.22-2.87 (m, 6H), 2.33-2.19 (m, 2H), 1.45-1.40 (m, 6H). LC-MScalculated for C₂₅H₂₅ClF₃NO₄S₂ [M+] 560; Observed: 257 (M⁺-303).

EXAMPLE 484N-(2,5-difluorophenyl)-4-(ethylsulfanyl-N-((1R)-{2-[3-(ethylsulfanyl)propyl]-4-fluorophenyl}ethylbenzenesulfonamide

R_(f)=0.49 (5:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.68-7.50 (m, 2H), 7.29-7.21 (m, 2H0, 7.04-6.33 (m, 6H), 5.88-5.76 (m,1H), 3.21-3.11 9m, 1H0, 2.98 9q, 2H0, 2.83-2.71 (m, 1H), 2.68-2.56 (moverlaps q, 4H), 1.95-1.93 9m, 2H), 1.52-1.49 (br, 3H0, 1.33 (t, 3H),1.27 (t, 3H). LC-MS cacld for C₂₇H₃₀F₃NO₂S₃: 553. Observed: 576 (M++Na).

EXAMPLE 485 Methyl(2R)-2-[(tert-butoxycarbonyl)amino]-3-({3-[2-(1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]propyl}sulfanyl)propanoate

R_(f)=0.50 (3:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.71-7.58 (m, 2H), 7.45-7.40 (m, 2H), 7.00-6.45 (m, 6H), 5.87 (q, 1H),4.45-5.40 (br, 1H), 4.61 (br, 1H), 3.78, 3.76 (s, rotomers, 3H),3.30-3.00 (m, 3H), 2.81-2.65 (m, 3H), 1.94-1.88 (m, 2H), 1.52-1.38 (broverlaps s, 12H). LC-MS cacld for C₃₂H₃₆ClF₃N₂O₆S₂: 701. Observed: 398(MW-303).

EXAMPLE 486 Methyl(2R)-2-[(tert-butoxycarbonyl)amino]-3-{3-[2-(1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]propyl]sulfonyl)propanoate

R_(f)=0.38 (2:1; hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.71-7.61 (m, 2H), 7.50-7.41 (m, 2H), 7.11-6.49 (m, 6H), 5.89 (q, 1H),5.71 (br, 1H), 3.81, 3.79 (s, rotomers, 3H), 3.74-3.70 (m, 2H),3.24-3.20 9m, 3H), 2.91 (br, 1H), 2.28-2.17 (m, 2H0, 1.45-1.45 (broverlaps s, 12H). LC-MS cacld for C₃₂H₃₆ClF₃N₂₀S₂: 733. Observed: 633(M⁺-Boc).

EXAMPLE 487 Methyl(2R)-2-amino-3-({3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]propyl}sulfonyl)propanoateHydrochloride

R_(f)=0.43 (2:1; hexanes:ethyl acetate). ¹H NMR (CD₃OD) δ (ppm):7.81-7.51 (m, 4H), 7.70-6.85 (m, 4H), 6.66-6.45 (m, 2H), 5.94-5.89 (m,1H), 4.2 9br, 1H), 3.76-2.92 (s overalaps m, 9H), 2.21-2.11 (m, 2H),1.51-1.46 (br, 3H). LC-MS cacld for C₂₇H₂₆ClF₃N₂O₆S₂: 632. Observed: 633(MH⁺).

EXAMPLE 4884-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-(methylsulfanyl)butyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.33 (9:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.67-7.57 (m, 2H), 7.43-7.37 (m, 2H), 7.02-6.312 (m, 6H), 5.86 (q, 1H),3.1 (br, 1H), 2.70-2.59 (m, 3H), 2.14 (s, 3H), 1.77-1.75 (m, 4H),1.55-1.53 (br, 3H). LC-MS cacld for C₂₅H₂₅ClF₃NO₂S₂: 528. Observed: 225(M⁺-303).

EXAMPLE 4894-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-(methylsulfonyl)butyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.52 (1:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.70-7.62 (m, 2H), 7.49-7.38 (m, 2H), 7.02-6.24 (m, 6H), 5.88 (q, 1H),3.30-3.07 (m, 3H), 2.96 (s, 3H), 2.88-2.70 (m, 1H), 2.10-1.86 (m, 4H),1.52 (d, 3H). LC-MS cacld for C₂₅H₂₅ClF₃NO₄S: 560. Observed: 578(M⁺+H₂O).

EXAMPLE 4904-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[4-(ethylsulfanyl)butyl]-4-fluorophenyl}ethyl)benzenesulfonamide

R_(f)=0.33 (9:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.68-7.58(m, 2H), 7.45-7.38 (m, 2H), 6.99-6.31 (m, 6H), 5.85 (q, 1H), 3.1 (br,1H), 2.70-2.61 (m, 3H), 2.57 (q, 2H), 1.78-1.73 (m, 2H), 1.53 (br, 3H),1.28 (t, 3H). LC-MS cacld for C₂₆H₂₇ClF₃NO₂S₂: 542. Observed: 239(M⁺-303).

EXAMPLE 4914-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-}2-[4-(ethylsulfonyl)butyl]-4-fluorophenyl}ethyl)benzenesulfonamide

R_(f)=0.14 (3:1;hexanes:ethyl acetate). ¹H NMR (CDCl₃) δ (ppm):7.71-7.63 (m, 21H), 7.48-7.36 (m, 2H), 7.02-6.31 (m, 6H), 5.87 (q, 1H),3.31-3.22 (m, 3H), 3.06 (q, 2H), 2.17-1.67 (m, 4H), 1.48 (d, 3H), 1.41(t, 3H). LC-MS cacld for C₂₆H₂₇ClF₃NO₄S₂: 574. Observed: 592 (M⁺+1120).

EXAMPLE 492

Numerous compounds according to the invention can be prepared employingthe general scheme set forth in SCHEME 492.

In an oven-dried two necked 100 mL round bottom flask under a vigorousstream of Ar was placed a solution of (R)—Oxazaborolidine in toluene(5.5 mL 1.27 M, 7 mmol, Strem). To this solution was slowly addedBH₃.Me₂S solution (8.3 mL, 83 mmol, 10.0 M, Aldrich). The reactionmixture was then cooled to −20° C. and neat ketone (30.0 g, 138 mmol,Marshalton) was added through a syringe pump over a period of 4-5 hwhile keeping the bath temperature at −20° C. After the addition wascomplete the reaction mixture was allowed to stir at −20° C. until thereaction was complete by GC (about 2 h). The reaction mixture was thencarefully quenched by adding to pre-cooled methanol (−20° C.) andstirred for 1 h. The reaction mixture was then concentrated underreduced pressure and the crude product was purified by filtrationthrough silica gel by eluting with 10:1-1:6 hexanes:ethyl acetate toseparate the product from the catalyst. Isolated quantitative yield ofthe product. R_(f) (10:1 hexanes:ethyl acetate) 0.32. ¹H NMR (CDCl₃) δ7.60-7.57 (dd, 1H), 7.27-7.31 (m, 2H), 7.10-7.00 (m, 1H), 5.30-5.17 (dq,1H), 1.99 (s, 1H), 1.49 (d, 3H).

Ethyl vinylacetate (27.98 g, 218.3 mmol) was dissolved in 100 mL of dryTHF, in an oven dried flask. The flask was cooled in an ice bath and asolution of 9-BBN (0.5 M, 437 mL, 218.5 mmol, Aldrich) was added over aperiod of 1 h. The reaction mixture was allowed to stir at roomtemperature for 8 h and then added K₂CO₃ (70.0 g, 506 mmol), DMF (700mL), alcohol (40 g, 182 mmol) and PdCl₂dppf (4.0 g, 2.7 mol %, Aldrich).The reaction mixture was heated to 60° C. for 21 h at which time TLCshows complete consumption of the alcohol. The reaction mixture was thencooled to room temperature, filtered through celite and concentrated.The crude reaction mixture was purified by chromatography over SiO₂ (1.0Kg of SiO₂, 5:1 hexanes:ethyl acetate) to isolate 37 g of pale yellowoil (95% pure). ¹H NMR (CDCl₃) δ 7.52-7.50 (dd, 1H), 6.96-6.82 (m, 3H),5.15-5.11 (br q, 1H), 4.13-4.06 (q, 2H), 2.75-2.63 (m, 2H), 2.35 (t,2H), 1.93 (p, 2H), 1.48 (d, 3H), 1.23 (t, 3H).

EXAMPLE 493 Ethyl4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)₅-fluorophenyl]butanoate

To a solution of PPh₃ (41.2 g, 157 mmol, Aldrich), in 180 mL of drytoluene was added solid sulfonamide 1 (47.6 g, 157 mmol). The solutionwas stirred at room temperature for 30 min (sulfonamide dissolves onlypartially) and cooled to 0° C. in an ice-bath. Neat DEAD (24.7 mL, 157mmol, Aldrich) was slowly added to the reaction mixture. The sulfonamidedissolves as the addition of DEAD progresses. After the addition wasover, the reaction mixture was allowed to warm to room temperature and asolution of the alcohol (37 g, 131 mmol) in 80 mL of dry toluene wasadded through a syringe pump over a period of 5 h The reaction mixturewas then allowed to stir at room temperature until TLC shows completeconsumption of starting material (21 h). The reaction mixture was thenconcentrated under reduced pressure. The phosphine oxide wascrystallized from 6:1 hexanes:ethyl acetate and the mother liquor wasconcentrated and purified by chromatography (7:1 hexanes:ethyl acetate)to isolate 51 g of product as pale yellow oil. R_(f) (10:1 hexanes:ethylacetate) 0.33 ¹H NMR (CDCl₃) δ7.65-7.58 (m, 2H), 7.41-7.39 (m, 2H),7.15-6.31 (m, 6H), 5.82 (q, 1H), 4.16 (q, 2H), 3.10 (m, 1H), 2.68 (m,1H), 2.4 (t, 2H), 1.93 (m, 2H), 1.52-1.45 (br 3H), 1.45 (t, 3H).

EXAMPLE 4944-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)5-fluorophenyl]butanoic Acid

A solution of the ester (48 g, in 700 mL of methanol) was cooled to 0°C. and 230 mL of LiOH solution (10.2 g of LiOH in 230 mL of water) wasadded slowly. The reaction mixture turned turbid, and a pale yellowprecipitate separates. The reaction mixture was mechanically stirred at0° C. for 1 h and at room temperature for 2 h. The reaction mixture wasthen cooled to 0° C. and carefully adjusted to pH1 with 6 N HCl.Extracted the product with 4×250 mL of ethyl acetate, washed the ethylacetate solution with dilute brine (3×200 mL), dried the organic layerwith MgSO₄, filtered and concentrated to yield crude product. The crudeproduct was purified by SiO₂ chromatography (1:1 hexanes:ethyl acetate)and the product was recrystallized from 4:1 hexanes:ethyl acetate (10mL/g) to >98% ee. R_(f ()10:4 hexanes:ethyl acetate) 0.15. ¹H NMR(CDCl₃) 5.66-7.59 (m, 2H), 7.43-7.40 (m, 2H), 6.99-6.33 (m, 6H), 5.85(q, 1H), 3.15-3.11 (m, 1H), 2.78-2.68 (m, 1H), 2.54 (t, 2H), 2.02 (m,2H), 1.54-1.52 (br d, 3H).

EXAMPLE 495

Using the scheme outlined in the preparative scheme in this example, theof Example 496-503 compounds were prepared.

EXAMPLE 4964-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-cyclohexylbutanamide

R_(f)=0.39 (2:1 hexanes:ethyl acetate) ¹H NMR (300 MHz, CDCl₃) δ (ppm):7.70-7.59 (m, 2H), 7.47-7.41 (m, 2H), 7.01-6.32 (m, 6H), 5.92-5.85 (q,1H), 5.62 (br, 1H), 3.86-3.74 (m, 1H), 3.12-3.03 (m, 1H), 2.80-2.70 (m,1H), 2.38-2.28 (m, 2H), 2.01-1.92 (br, 4H), 1.73-1.07 (m, 1H). LC-MScalculated for C₃₀H₃₂ClF₃N₂O₃S [MH+] 593; Observed: 290 (−303).

EXAMPLE 4974-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N,N-diethylbutanamide

R_(f)=0.35 (2:1 hexanes:ethyl acetate) ¹H NMR (300 MHz CDCl₃) δ (ppm):7.70-7.61 (m, 2H), 7.45-7.43 (br, 2H), 7.00-6.32 (br, 6H), 5.93-5.87 (q,1H), 3.46-3.32 (m, 4H), 3.18-3.11 (m, 1H), 2.75-2.70 (m, 1H), 2.51-2.46(t, 2H) 2.05-1.95 (m, 2H), 1.51-1.49 (br, 3H), 1.26-1.12 (m, 6H). LC-MScalculated for C₂₈H₃₀ClF₃N₂O₃S [H+] 567; Observed: 567.

EXAMPLE 4984-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-methylbutanamide

R_(f)=0.17 (1:1 hexanes:ethyl acetate) ¹H NMR (300 MHz CDCl₃) δ:7.71-7.60 (m, 2H), 7.48-7.41 (m, 2H), 7.00-6.30 (m, 6H), 5.93-5.86 (q,1H), 5.80 (br, 1H), 3.13-3.03 (m, 1H), 2.85-2.74 (m, 4H), 2.40-2.35 (t,2H), 2.02 (br, 2H), 1.50-1.47 (hr, 3H). LC-MS calculated forC₂₅H₂₄ClF₃N₂O₃S [MH+] 525; Observed: MH-303.

EXAMPLE 499 4-[2-((1R)-1-{[(4chlorophenyl)sulfonyl]-2,5-difluoroanilno}ethyl)-5-fluorophenyl]-N-ethylbutanamide

R_(f)=0.31 (1:1 hexanes:ethyl acetate) ¹H NMR (300 MHz CDCl₃) δ:7.70-7.60 (m, 21), 7.48-7.41 (m, 2H), 7.00-6.31 (m, 6H), 5.93-5.86 (q,1H), 5.73 (br, 1H), 3.38-3.28 (m, 2H), 3.13-3.03 (m, 1H), 2.78-2.73 (m,1H), 2.38-2.33 (t, 2H), 2.02-2.01 (br, 2H), 1.50-1.47 (br, 3H),1.18-1.13 (t, 3H). LC-MS calculated for C₂₆H₂₆ClF₃N₂O₃S MH+] 539;Observed: MH-303.

EXAMPLE 5004-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N,N-dipropylbutanamide

R_(f)=0.46 (3:1 hexanes:ethyl acetate) ¹H NMR (300 MHz CDCl₃) δ:7.70-7.61 (m, 2H), 7.45-7.43 (m, 2H), 7.00-6.31 (m, 6H), 5.93-5.86 (q,1H), 3.34-3.11 (m, 5H), 2.75-2.70 (m, 1H), 2.51-2.46 (t, 2H), 2.04-1.97(m, 2H), 1.65-1.49 (m, 7H), 0.95-0.88 (m, 6H). LC-MS calculated forC₃₀H₃₄ClF₃N₂O₃S [MH+] 595; Observed: 595.

EXAMPLE 5014-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-oxo-4′-(1-piperidinyl)butyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.31 (2:1 hexanes:ethyl acetate) ¹H NMR (300 MHz CDCl₃) δ7.70-7.60(m, 2H), 7.46-7.43 (m, 2H), 7.00-6.32 (m, 6H), 5.92-5.85 (q, 1H),3.62-3.58 (t, 2H), 3.47-3.43 (t, 2H), 3.15-3.11 (m, 1H), 2.78-2.68 (m,1H), 2.52-2.47 (t, 2H), 2.03-1.93 (m, 2H), 1.66-1.49 (m, 9H). LC-MScalculated for C₂₉H₃₀ClF₃N₂O₃S [MH+] 579; Observed: 579.

EXAMPLE 5024-Chloro-N-(2,5-difluorophenyl-N-((1R)-1-{4-fluoro-2-[4-oxo-4-(4-thiomorpholinyl)butyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.38 (2:1 hexanes:ethyl acetate) ¹H NMR (300 MHz CDCl₃) δ7.70-7.60(m, 2H), 7.47-740 (m, 2H), 7.01-6.31 (m, 6H), 5.94-5.87 (q, 1H),3.94-3.91 (t, 2H), 3.81-3.78 (t, 2H), 3.12-3.10 (m, 1H), 2.84-2.71 (m,1H), 2.65-2.64 (br, 4H), 2.53-2.49 (t, 2H), 2.06-1.96 (m, 2H), 1.49-1.47(br, 3H). LC-MS calculated for C₂₈H₂₈ClF₃N₂O₃S₂ [MH+] 597, Observed 597.

EXAMPLE 5034-Chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-(4-thiomorpholinylsulfonyl)butyl]phenyl}ethyl)benzenesulfonamide

R_(f)=0.46 (1:1 hexanes:ethyl acetate) ¹H NMR (300 MHz CDCl₃) δ:7.71-7.59 (m, 2H), 7.51-7.41 (m, 2H), 7.07-6.29 (m, 6H), 5.96-5.94 (br,1H), 4.14-4.04 (d, 4H), 3.07-2.83 (m, 6H), 2.64-2.59 (t, 2H), 2.08-2.03(m, 2H), 1.44-1.42 (d, 3H). LC-MS calculated for C₂₉H₂₈ClF₃N₂O₅S₂ [MH+]629; Observed. MH-303.

EXAMPLE 504 General Procedure for the Synthesis of Amine Oxides

The free base (0.5 g) was dissolved in methanol (5 mL) and 30% H₂O₂ inwater (5 mL) was added. The mixture was stirred at room temperature for14 h then concentrated under reduced pressure. The resulting crudeproduct was purified by chromatography on SiO₂ to yield the desiredN-oxide product in >90% yield.

Using the preparative scheme described in the previous example, thefollowing compounds were prepared.

EXAMPLE 5054-Chloro-N-{2-[3-(1-hydroxy-1˜lambda˜5˜piperidin-1-yl)propoxy]benzyl}-N-phenylbenzenesulfonamide

R_(f)=0.15 (1% triethylamine/5% methanol/ethyl acetate) ¹H NMR (300 MHz,CDCl₃) δ (ppm): 7.55 (m, 4H), 7.21 (m, 4H), 6.78 (m, 4H), 6.60 (m, 1H),4.74 (s, 2H), 4.53 (m, 2H), 4.19 (m, 4), 3.53 (t, 2H), 2.67 (m, 2H),2.35 (m, 2H), 1.87-1.27 (m, 4H). ¹³C NMR (75 MHz, CDCl₃) δ (ppm): 156.9,139.6, 137.2, 136.0, 131.9, 130.1, 129.4, 129.0, 128.9, 128.8, 128.5,121.5, 1202, 110.7, 66.5, 64.6, 63.6, 51.3, 29.7, 22.1, 21.3, 20.3. ESIcalculated for C₂₇H₃₁ClN₂O₄S [MH+] 515; Observed: 515.

EXAMPLE 5064-Chloro-N-2,5-dichlorophenyl)-N-{2-[3-(1-oxido-1-piperidinyl)propoxy]benzyl}benzenesulfonamide

R_(f)=0.42 (10% methanol/DCM) ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.64-751(m, 4H), 7.26-7.14 (m, 4H,), 6.81-6.03 (m, 3H), 4.97-4.80 (dd, 2H),4.47-4.17 (m, 6H), 3.45 (m, 2H), 2.64 (m, 2H), 2.28 (m, 2H), 1.86 (m,3H), 1.49 (m, 1H). ¹³C NMR (75 MHz, CDCl₃) δ (ppm): 157.3, 140.3, 137.3,135.8, 134.1, 132.8, 132.4, 131.8, 131.6, 131.0, 130.5, 129.9, 129.3,121.2, 120.8, 111.2, 66.9, 65.1, 64.6, 63.5, 50.42, 22.5, 21.6, 20.7.

EXAMPLE 5074-Chloro-N-(2,5-difluorophenyl-N-{2-[3-(1-oxido-1-pyrrolidinyl)propoxy]benzyl}benzenesulfonamide

R_(f)=0.38 (9% methanol/DCM) ¹H NMR (500 MHz, CD₃OD) δ (ppm): 7.69-7.61(m, 4H), 7.18 (m, 1H), 7.01-6.89 (m, 4H), 6.77-6.67 (m, 2H), 4.13 (t,2H), 3.81 (m, 2H), 3.64-3.48 (m, 4H), 2.52-2.33 (m, 4), 2.09 (m, 2H).¹³C NMR (125 MHz, CD₃OD) δ (ppm): 160.4, 159.1, 158.7, 158.4, 157.1,140.9, 138.5, 132.8, 131.4, 130.8, 130.5, 127.6, 123.5, 121.4, 120.1,119.9, 118.5, 118.4, 118.4, 118.3, 118.2, 118.1, 112.3, 69.1, 66.8,66.4, 51.0, 25.6, 22.7. ESI calculated for C₂₆H₂₇ClF₂N₁O₄S [MH+] 537;Observed: 537.

EXAMPLE 5084-Chloro-N-(2,5-difluorophenyl)-N-[2-[3-(1,1,4-trioxido-4-thiomorpholinyl)propoxy]benzyl}benzenesulfonamide

R_(f)=0.53 (9% methanol/DCM) ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.65-7.48(m, 4H), 7.32-7.16 (m, 1H), 6.91-6.58 (m, 6H), 4.78 (s, 2H), 4.39-3.92(m, 8H), 3.65 (m, 2H), 2.96 (m, 2H), 2.64 (m, (2H), ¹³C NMR (75 MHz,CDCl₃) δ (ppm): 159.3, 157.9, 156.9, 156.1, 154.5, 139.7, 136.6, 131.4,130.3, 129.4, 128.7, 125.7, 125.6, 125.4, 121.5, 120.4, 118.9, 118.5,117.2, 117.1, 117.0, 116.9, 116.8, 116.7, 110.8, 69.4, 65.5, 63.4, 50.0,46.3, 23.0. ESI calculated for C₂₆H₂₇ClF₂O₆S₂N₂ [MH+] 601; Observed:601.

EXAMPLE 5094-Chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-oxido-1-piperidinyl)propoxy]benzyl}benzenesulfonamide

R_(f)=0.45 (9% methanol/DCM) ¹H NMR (300 MHz, CD₃OD) δ (ppm): 7.68-7.54(m, 4H), 7.23-6.67 (m, 6H), 6.29-6.22 (m, 2H), 4.26 (m, 2H), 3.70-3.48(m, 4H), 3.06 (m, 2H), 2.41 (m, 2H), 2.01-1.51 (m, 9H). ¹³C NMR (75 MHz,CD₃OD) δ (ppm): 158.9 (dd), 157.2, 155.6, (dd), 140.2, 137.0, 131.8,130.8, 129.9, 129.1, 125.7 (dd), 121.5, 120.7, 118.8 (d), 117.7, (t),11.4 (t), 111.2, 66.8, 65.0, 64.5, 50.6, 22.5, 21.6, 20.7. ESIcalculated for C₂₇H₂₉ClF₂N₂O₄S [MH+] 551; Observed: 551.

EXAMPLE 5104-Chloro-N-{2-[3-(diethylnitroryl)propoxy]benzyl}-N-(2,5-difluorophenyl)benzenesulfonamide

R_(f)=0.49 (9% methanol in DCM), ¹H NMR (300 MHz, CD₃OD) δ (ppm) (d,2H), 7.61 (d, 2H), 7.19 (t, 1H), 7.02-6.99 (m, 2H), 6.95 (d, 1H), 6.89(d, 1H), 6.78-6.70 (m, 2H), 4.83 (s, 2H), 4.12 (t, 2H0, 3.69-3.66 (m,2H), 3.44-3.40 (m, 4H), 2.37-2.34 (m, 2H), 1.37 (t, 6H). MS calculatedfor C₂₆H₂₉ClF₂N₂O₄S: 539; Observed: 539.

EXAMPLE 511 General Procedure for the Synthesis of Quaternary AmmoniumCompounds

The free base was dissolved in DCM (2 mL/mmol) and excess of MeI (4.0eq) was added. The reaction mixture was stirred at room temperature for1 h then concentrated under reduced pressure to give pure quaternaryammonium compounds.

EXAMPLE 5121-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-1-methylpiperidiniumIodide

R_(f)=0.42 (3:1:1 n-BuOH/H₂O/AcOH) ¹H NMR (300 MHz, CD₃OD) δ (ppm):7.69-7.57 (m, 4H), 7.18-6.59 (m, 7H), 4.80 (s, 2H), 4.16 (t, 2H), 3.88(m, 2H), 3.59 (m, 411, 3.18 (s, 2H), 2.37 (m, 2H), 1.93-1.60 (m, 6H).

EXAMPLE 5131-{3-[2-({2,5-dichloro[(4-chlorophenyl)sulfonyl]anilino}methyl)phenoxy]propyl}-1-methylpiperidiniumIodide

R_(f)=0.32 (10:1;DCM:methanol). ¹H NMR (300 MHz, CD₃OD) δ(ppm):7.74-7.63 (m, 4H), 7.28-7.18 (m, 3H), 6.93 (d, 1H), 6.86 (d, 1H),6.75 (dd, 1H), 6.64 (dt, 1H), 5.13 (d, 1H), 4.67 (d, 1H), 4.27-4.26 (m,1H), 4.11-4.02 (m, 2H), 3.86-3.79 (m, 1H), 3.52 (br m, 4H), 3.22 9s,3H), 2.40-(br m, 2H), 1.99-1.64 (m, 6H). MS ESI calculated forC₂₉H₃₂Cl₃N₂O₃S: 581. Observed 581.

EXAMPLE 514

Compounds of the present invention can be prepared using the followinggeneral schemes.

In Schemes 514a, 514b and 514c, R¹ is halogen,methyloxytetrahydropyranyl, or a methyloxyacyl moiety such as —CH₂OAc.R² is hydrogen or halogen; R³ is hydrogen, halogen or substituted orunsubstituted alkyl; R⁴ and R⁵ are substituted or unsubstitutedhydrocarbyl, substituted or unsubstituted heterocycle optionally havingone or more double bonds, alkoxy, ether, ester, amide, R⁶ is substitutedor unsubstituted hydrocarbyl, or substituted or unsubstitutedheterocycle optionally having one or more double bonds; n is an integerfrom 1 up to 4, and Z is heterocycle optionally having one or moredouble bonds.

Scheme 514a illustrates a general process and shows the production ofchiral compounds of a key intermediate of Formula II.

The Scheme process begins with reduction of2,5-disubstituted-nitrobenzene (III) to the corresponding substitutedaniline (IV) which is reacted with an Re-substituted benzenesulfonylhalide to provide intermediate (V). Treatment of (V) with(S)₄[[dimethyl(1,1-dimethylethyl)silyl]oxy]-2-alkanol gives compound VIIwhich is converted, in turn, to the corresponding alcohol (VIII) andthen to the halide (II) with bromide being the preferred halide.

Scheme 514b illustrates several methods of producing some of the FormulaI products; i.e., when R¹ is halogen, —CH₂O-2-tetrahydropyran or—CH₂OAc.

In Scheme 514b, products (Ia) can be obtained starting with intermediatecompound (II). Products (Ia) can be formed directly from intermediatecompound (II) by reaction with nucleophilic heterocyclics.Alternatively, intermediate compound (II) can be converted intocompounds (X and XI), which can then be used to produce products (Ia) asshown in Scheme 2.

Scheme 514c shows preparation of Formula I products wherein R¹ is—CH₂OH.

In Scheme 514c, cleavage of acetyl or tetrahydropyran groups fromcompounds of Formula Ia provide Formula Ib products wherein R¹ is—CH₂OH.

EXAMPLE 515

In the following examples, intermediate alcohols were prepared via aMitsunobu reaction between a secondary sulfonamide and a commerciallyavailable TBDMS protected chiral diol, followed by HF deprotection asdescribed herein.

4-Chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-2-hydroxyethyl]benzenesulfonamide

Yield=70%; Colorless viscous oil: IR (neat, CH₂Cl₂) 1504, 1346, 1164,1093, 755, 625 cm⁻¹; MS (ESI+), 362 (M+H)⁺.

EXAMPLE 5164-Chloro-N-2,5-difluorophenyl)-N-[2-[[[[4-nitrophenyl]oxy]carbonyl]oxy](—R)-1-methylethyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-2-hydroxyethyl]benzenesulfonamide(958 mg, 2.65 mmol) in THF (13 mL) and acetonitrile (2 ml) was addedpyridine (209 mg, 2.65 mmol) followed by 4-nitrophenyl chloroformate(586 mg, 2.92 mmol). The resulting mixture was allowed to stir at 22° C.for 16 h. The solvents were removed and the product was dissolved inether, washed with water, then brine. The ether layer was dried overMgSO₄, filtered, and concentrated under reduced pressure. Silica gelchromatography (ethyl acetate:hexane, 5-20% ethyl acetate gradient) ofthe concentrate afforded the title compound (1.23 g, yield 88%) as acolorless viscous oil.

EXAMPLE 517 4-Chloro-N-(2,5-difluorophenyl)-N-[2-[[N′-[3-(1h-imidazol-1-yl)propylamino]carbonyl]oxy]-(r)-1-methylethyl]benzenesulfonamide

To a solution of4-chloro-N-2,5-diflurophenyl)-N-[2-[[[[4-nitrophenyl]oxy)carbonyl]oxy]-1(R)-methylethyl]benzenesulfonamide(580 mg, 1.10 mmol) in methanol (5 ml) was added3-aminopropyl-(1H)imidazole (276 mg, 2.20 mmol). The resulting mixturewas allowed to stir at 22° C. for 16 h, then concentrated under reducedpressure. Silica gel chromatography (methanol in CH₂Cl₂ with 0.5% NH₄OH,5-10% methanol gradient) of the concentrate afforded the title compound(344 mg, 61%) as a pale yellow powder. IR (KBr) 1722, 1506, 1345, 1261,1183, 623 cm⁻¹; MS (ESI+), 513 (M+H)⁺.

Non basic carbamates shown in the following examples were prepared in ananalogous manner as described above but were purified via silica gelchromatography (ethyl acetate:hexane 5-50% ethyl acetate gradient) ofthe concentrate.

EXAMPLE 5184-Chloro-N-(2,5-difluorophenyl)-N-[2-[[[pyrrolidin-1-yl]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=87%; Colorless viscous oil: IR (neat, CH₂Cl₂) 1704, 1504, 1424,1352, 1165, 1092 cm⁻¹; MS (ESI+), 459 (M+H)⁺.

EXAMPLE 5194-Chloro-N-(2,5-dichlorophenyl-N-[2-[[N′-[3-(1H-imidazol-1-yl)propylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=81%; pale yellow powder: IR (neat, CH₂Cl₂) 1718, 1467, 1250, 1169,1085, 622 cm⁻¹; MS (ESI+), 545 (M+H)⁺.

EXAMPLE 5204-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[[pyrrolidin-1-yl]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=81%; White solid: IR (KBr) 1702, 1430, 1352, 1174, 1099, 620 cm⁻¹;MS (ESI+), 491 (M+H)⁺.

EXAMPLE 5214-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[[(S)-2-(hydroxymethyl)pyrrolidin-1-yl)]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=81%; Colorless glassine solid: IR (KBr) 1699, 1421, 1356, 1170,1095, 622 cm⁻¹; MS (ESI+), 521 (M+H)⁺.

EXAMPLE 5224-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[N′-[2-(piperidin-1-yl)ethylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=73%; Colorless glassine solid: IR (neat, CH₂Cl₂) 1723, 1468, 1352,1170, 1095, 622 cm⁻¹; MS (ESI+), 548 (M+H)⁺.

EXAMPLE 5234-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[[N′-[3-(1h-imidazol-1-yl)propyl-N′-Ethylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=48%; Pale yellow viscous oil: IR (neat, CH₂Cl₂) 1699, 1467, 1352,1170, 1095, 623 cm⁻¹; MS (ESI+), 573 (M+H)⁺.

EXAMPLE 5244-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[N′-[3-(1H-tetrazol-1-yl)-propylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=46%; White powder: IR (KBr) 1718, 1467, 1348, 1168, 1095, 622cm⁻¹; MS (ESI+), 547 (M+H)⁺.

EXAMPLE 5254-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[N′-[2-(hydroxyethyl)-N′-methyl]amino]carbonyl]oxy](R)-1-methylethyl]benzenesulfonamide

Yield=80%; Pale yellow viscous oil: IR (neat, CH₂Cl₂) 1699, 1466, 1354,1170, 1095, 623 cm⁻¹; MS (ESI+), 495 (M+H)⁺.

EXAMPLE 5264-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[[N′-[3-(1H-imidazol-1-yl)propyl]-N′-methylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=50%; Pale yellow gummy solid: IR (neat, CH₂Cl₂) 1699, 1467, 1352,1170, 1095, 622 cm⁻¹; MS (ESI+), 559 (M+H)⁺.

EXAMPLE 5274-Chloro-N-(2-fluoro-5-chlorophenyl)-N-[(R)-1-methyl-2-hydroxyethyl]benzenesulfonamide

Yield=83%; Colorless viscous oil: IR (neat, CH₂Cl₂) 1493, 1345, 1166,1054, 758, 622 cm⁻¹; MS (ESI+), 378 (M+H)⁺.

EXAMPLE 5284-Chloro-N-(2-fluoro-5-chlorophenyl)-N-[2-[[[pyrrolidin-1-yl]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=71%; White powder: IR (neat, CH₂Cl₂) 1704, 1494, 1424, 1352, 1171,622 cm⁻¹; MS (ESI+), 475 (M+H)⁺.

EXAMPLE 5294-Chloro-N-(2-fluoro-5-chlorophenyl)-N-[2-[[N′-[3-(1H-imidazol-1-yl)propylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=81%; White powder: IR (KBr) 1720, 1345, 1263, 1171, 758, 620 cm⁻¹;MS (ESI+), 529 (M+H)⁺.

EXAMPLE 5304-Chloro-N-(2-fluoro-5-chlorophenyl)-N-[2-[[N′-[2-(1H-imidazol4-yl)ethylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield-74%; White powder: IR (KBr) 1716, 1494, 1262, 1169, 1091, 758cm⁻¹; MS (ESI+), 515 (M+H)⁺.

EXAMPLE 5314-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[2-[[N′-[3-(1H-imidazol-1-yl)propylamino]carbonyl]oxy]-(1R)-(2R)-dimethylethyl]benzenesulfonamide

Yield=77%; White solid: IR (KBr) 1716, 1347, 1168, 1091, 757, 627 cm⁻¹;MS (ESI+), 55 (M+H)⁺.

EXAMPLE 5324-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[2-[[[N′-[3-(1H-imidazol-1-yl)propyl]-N′-cyclopropylmethylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=32%; Colorless glassine solid: IR (KBr) 1697, 1477, 1167, 1092,758, 622 cm⁻¹; MS (ESI+), 595 (M+H)⁺.

EXAMPLE 5334-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[2-[[[N′-[3-(1H-imidazol-1-yl)propyl]-N′-(2-methylethyl)amino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=43%; Beige solid: IR (neat, CH₂Cl₂) 1342, 1166, 1092, 1055, 757,622 cm⁻¹; MS (ESI+), 583 (M+H)⁺.

EXAMPLE 534 4-Chloro-N-(2dichlorophenyl)-N-[1-(S)-[1-[2-(methylsulfonyl)ethyl]pyrrolidin-2-yl]ethyl]benzenesulfonamide

The above-named compound was prepared using the preparative schemedescribed below.

α-Methyl-[N-(tert-butoxycarbonyl)]-L-prolinol

To a solution of (S)-2-acetyl-1-pyrrolidinecarboxylic acid1,1-dimethylethyl ester [CA 91550-08-2] (5.600 g, 26.400 mmol) inethanol (40 mL) was added sodium borohydride (2.0 g, 53 mmol) undernitrogen at 0° C. The reaction was stirred for 2 h. Ethanol was removedunder reduced pressure. The concentrate was diluted with ethyl ether(100 mL) and washed with H₂O (2×100 mL). The organic extract was driedover Na₂SO₄, filtered, and concentrated. Silica gel chromatography (1:5to 1:4 gradient; ethyl acetate/hexanes) of the concentrate afforded twoisomers, designated A, the first eluting isomer, (2.050 g, 40%) and themore polar B (1.537 g, yield=30%), of the title compound. Isomer B wasused in the subsequent reaction.

4-Chloro-N-(2,5-dichlorophenyl)-N-[1-(S)-[1-[(1,1-dimethylethoxy)carbonyl]pyrrolidin-2-yl]ethyl]benzenesulfonamide

To a solution of 4-chloro-N-(2,5-dichlorophenyl)benzenesulfonamide(0.100 g, 0.298 mmol), triphenylphosphine (0.230 g, 0.890 mmol),α-methyl-[N-(tert-butoxy carbonyl)]-L-prolinol, (isomer B, 0.200 g,0.890 mmol) in toluene (2 mL) was added diisopropylazodicarboxylate(0.180 g, 0.890 mmol) dropwise at 0° C. under nitrogen atmosphere. Theresulting mixture was allowed to warn to 22° C. with stirring. After 18h the mixture was washed with sat NaHCO₃ (4 mL), brine (4 mL) andextracted with ethyl ether (4 mL). The organic extract was dried overNa₂SO₄ and filtered. Silica gel chromatography (1:4 ethylacetate/hexanes) of the concentrate afforded the title compound (0.095g, yield=60%), MS (ESI) 532.

4-Chloro-N-(2,5-dichlorophenyl)-N-[1-(S)-pyrrolidin-2-yl]ethyl]benzeneSulfonamide

To a solution of4-chloro-N-(2,5-dichlorophenyl)-N-[1-(S)-[1-[(1,1-dimethylethoxy)carbonyl]pyrrolidin-2-yl]ethyl]benzenesulfonamide(0.095 g, 0.178 mmol) was added a solution of 1:1 trifluoroaceticacid/CH₂Cl₂ (2 mL) at 22° C. The mixture was stirred for 1 h at 22° C.The solvent and trifluoroacetic acid were removed by reduced pressure toafford the title compound (0.075 g, yield=98%), MS (ESI) 432.

4-Chloro-N-2,5-dichlorophenyl)-N-[1-(S)-[1-[2-(methylsulfonylethyl]pyrrolidin-2-yl]ethyl]benzenesulfonamide

To a solution of4-chloro-N-(2,5-dichlorophenyl)-N-[1-[(S)-pyrrolidin-2-yl]ethyl]benzenesulfonamide(0.075 g, 0.174 mmol) in THF (1 mL) was added methyl vinyl sulfone(0.060 g, 0.530 mmol) at 22° C. The reaction was stirred for 18 h. Theresulting mixture was washed with sat. K₂CO₃ (2 mL), brine (2 mL) andextracted with ethyl ether (2 mL). The organic solution was dried overNa₂SO₄, filtered and evaporated. Silica gel chromatography (1:5 ethylacetate/hexanes) of the concentrate afforded the title compound (0.533g, yield=57%), MS (ESI) 538.

EXAMPLE 535(R)-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(S)-[1-(methoxycarbonyl)-2-methylpropyl]amino]-1-methyl-5-oxopentyl]benzenesulfonamide

To a solution of(5R)—S-[N-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]-hexanoylchloride (0.265 g, 0.584 mmol) in THF (3 mL) was added Hunig's base(0.305 mL, 1.75 mmol) and L-valine methyl ester hydrochloride (0.294 g,1.75 mmol) at 22° C. The reaction was stirred at 22° C. temperature for12 h. The reaction was treated with sat. NaHCO₃ (6 mL) and the aqueousphase extracted with ether (3×15 mL). The combined organic extracts weredried over MgSO₄, filtered, and concentrated under reduced pressure.Silica gel chromatography (3:7 ethyl acetate:Hexanes) of the concentrateafforded the title compound as a light yellow wax (0.233 g, yield=73%).MS (ESI) 547 (M+H).

EXAMPLE 536(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(S)-[1-(carboxy)-2-methylpropyl]amino]-1-methyl-5-oxopentyl]benzenesulfonamide

To a solution of(R)₄-chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(S)-[1-(methoxycarbonyl)-2-methylpropyl]amino]-1-methyl-5-oxopentyl]benzenesulfonamide(0.170 g, 0.310 mmol) in methanol (3.5 mL) was added NaOH (1N, 0.450 mL,0.931 mmol) at 22° C. The resulting mixture was heated at reflux withstirring for 1.5 h. The mixture was acidified with 1N HCl and wasextracted with chloroform (3×20 mL). The combined organic extracts weredried over MgSO₄, filtered, and concentrated under reduced pressure toafford the title compound (0.161 g, 97%) as a white powder. MS (ESI) 533(M+H).

EXAMPLE 537(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[N-(S)-[1-(methoxycarbonyl)-2-methylpropyl]amino]1-methyl-4-oxobutyl]benzenesulfonamide

In a manner similar to the previous example, the title compound wasprepared by reacting(4R)-4-[N-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]pentanoylchloride with L-valine methyl ester hydrochloride (71% yield). MS (EST)533 (M+H).

EXAMPLE 538(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[N-(S)-[1-methoxycarbonyl)-3-methylbutyl]amino]-1-methyl-4-oxobutyl]benzenesulfonamide

In a manner similar to the previous example, the title compound wasprepared by reacting(4R)-4-[N-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]pentanoylchloride with L-leucine methyl ester hydrochloride (70% yield). MS (ES)547 (M+H).

EXAMPLE 539(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(R)-[1-(methoxycarbonyl)-2-methylpropyl]amino]-1-methyl-5-oxopentyl]benzenesulfonamide

In a manner similar to the previous example, the title compound wasprepared by reacting(5R)-5-N-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]hexanoylchloride with D-valine methyl ester hydrochloride (82% yield). MS (ESI)547 (M+H).

EXAMPLE 540(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(R)-[1-(methoxycarbonyl)-3-methylbutyl]amino]-1-methyl-5-oxopentyl]benzenesulfonamide

In a manner similar to the previous example, the title compound wasprepare by reacting(5R)-5-[N-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]hexanoylchloride with D-leucine methyl ester hydrochloride (73% yield). MS (ESI)561 (M+H).

EXAMPLE 541(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(S)-[1-methoxycarbonyl)-3-methylbutyl]amino]-1-methyl-5-oxopentyl]benzenesulfonamide

In a manner described herein, the title compound was prepared byreacting(5R)-5-[N-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]hexanoylchloride with L-leucine methyl ester hydrochloride to afford the titlecompound (71% yield). MS (ESI) 561 (M+H).

EXAMPLE 542(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[6-[N-(S)-[1-(methoxycarbonyl)-2-methylpropyl]amino]-1-methyl-6-oxohexyl]benzenesulfonamide

In a manner described herein, the title compound was prepared byreacting(6R)-6-[N-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]heptanoylchloride with L-valine methyl ester hydrochloride (85% yield). MS (ESI)561 (M+H).

EXAMPLE 543(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[6-[N-(S)-[1-(methoxycarbonyl)-3-methylbutyl]amino]-1-methyl-6-oxohexyl]benzenesulfonamide

In a manner described herein, the title compound was prepared byreacting(6R)-6-[N-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]heptanoylchloride with L-leucine methyl ester hydrochloride (89% yield). MS (ESI)575 (M+H).

EXAMPLE 544(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(R)-[1-(carboxy)-2-methylpropyl]amino]-1-methyl-5-oxopentyl]benzenesulfonamide

In a manner described herein, the title compound was prepared byhydrolysis of(R)-4-chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N—(R)-[1-(methoxycarbonyl)-2-methylpropyl]amino]-1-methyl-5-oxopentyl]benzenesulfonamide(90% yield). MS (ESI) 533 (M+H).

EXAMPLE 545(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(R)[1-(carboxy)-3-methylpropyl]amino]-1-methyl-5-oxopentyl]benzenesulfonamide

In a manner described herein, the title compound was prepared byhydrolysis of(R)-4-chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(R)-[1-(methoxycarbonyl)-3-methylbutyl]amino]-1-methyl-5-oxopentyl]benzenesulfonamide(89% yield). MS (ESI) 547 (M+H).

EXAMPLE 546(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(S)-[1-(carboxy)-3-methylbutyl]amino]-1-methyl-5-oxopentyl]benzenesulfonamide

In a manner described herein, the title compound was prepared byhydrolysis of(R)₄-chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(S)-[1-(methoxycarbonyl)-3-methylbutyl]amino]-1-methyl-5-oxopentyl]benzenesulfonamide(90% yield). MS (ESI) 547 (M+H).

EXAMPLE 547(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[6-[N-(S)-[1-(carboxy)-2-methylpropyl]amino]-1-methyl-6-oxohexyl]benzenesulfonamide

In a manner described herein, the title compound was prepared byhydrolysis of(R)-4-chloro-N-(5-chloro-2-fluorophenyl)-N-[6-[N-(S)-[1-(methoxycarbonyl)-2-methylpropyl]amino]-1-methyl-6-oxohexyl]benzenesulfonamide(85% yield). MS (ESI) 547 (M+H).

EXAMPLE 548(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[6-[N-(S)-[1-(carboxy)-3-methylbutyl]amino]-1-methyl-6-oxohexyl]benzenesulfonamide

In a manner described herein, the title compound was prepared byhydrolysis of(R)-4-chloro-N-(5-chloro-2-fluorophenyl)-N-[6-[N-(S)-[1-(methoxycarbonyl)-3-methylbutyl]amino]-1-methyl-6-oxohexyl]benzenesulfonamide(83% yield). MS (ESI) 561 (M+H).

EXAMPLE 5494-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[2-[[[(methylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

To a solution of4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[2-[[[[4-nitrophenyl]oxy]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide(50 mg, 0.08 mmol) in DMF (2.0 mL) in a 15 mL HDPE cartridge was addedmethylamine (5.2 mg,). The mixture was shaken for 12 h at 22° C. in a 48well reactor. The mixture was filtered, rinsed with ether to a test tubeand concentrated by speed vacuum to afford crude4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[2-[[[methylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide.The molecular weight of the intermediate product was determined byLC/MS. The residue was diluted with methanol (2.0 mL) in a test tube andK₂CO₃ was added. The mixture was shaken for 2 hours and filtered. Themethanol was removed by speed vacuum and the residue was purified bypreparative HPLC with 90% methanol/H₂O at 4 mL/min. The desired productwas concentrated by speed vacuum to afford the title compound. Yield=32%colorless oil: LC/MS, 448 (M+H); Retention Time, 3.71 min.

The following carbamates were prepared as described in the previousexample. They were all analyzed by LC/MS.

EXAMPLE 5504-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[2-[[[propylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=32% colorless oil: LC/MS, 476 (M+H); Retention time, 3.93 min.

EXAMPLE 5514-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[2-[[[(1,1-dimethyl)ethylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield-35% colorless oil: LC/MS, 490 (M+H); Retention time, 4.09 min.

EXAMPLE 5524-Chloro-N-[5-chloro-2-hydroxymethyl)phenyl]-N-[2-[[[diethylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=26% colorless oil: LC/MS, 490 (M+H); Retention time, 4.08 min.

EXAMPLE 5534-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[2-[[[cyclohexylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=15% colorless oil: LC/MS, 516 (M+H); Retention time, 4.23 min.

EXAMPLE 5544-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[2-[[N′-[3-(1H-imididazol-1-yl)propylamino]carbonyl]oxy](R)-1-methylethyl]benzenesulfonamide

Yield=30% colorless oil: LC/MS, 542 (M+H); Retention time, 4.80 min.

EXAMPLE 5554-Chloro-N-[5-chloro-2-hydroxymethyl)phenyl]-N-[2-[[[isopropylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=30% colorless oil: LC/MS, 476 (M+H); Retention time, 3.92 min.

EXAMPLE 5564-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[2-[[[pyrrolidin-1-yl]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=32% colorless oil: LC/MS, 488 (M+H); Retention time, 4.20 min.

EXAMPLE 5574-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[2-[[[(1-methyl)propylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=33% colorless oil: LC/MS, 490 (M+H); Retention time, 4.05 min.

EXAMPLE 5584-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[2-[[[ethylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

To a solution of4-chloro-N-[5-chloro-2-(acetoxymethyl)phenyl]-N-[2[[[[4-nitrophenyl]oxy]carbonyl]oxy]-(R)-methylethyl]benzenesulfonamide(0.85 g, 0.14 mmol) was added ethylamine (0.13 g, 0.28 mmol) in DMF (2mL). The resulting mixture was allowed to stir at 22° C. for 12 h andconcentrated under reduced pressure. The mixture was diluted withmethanol/H₂O (2 mL), followed by the addition of K₂CO₃. The mixture wasfiltered and the solvent was removed. Silica gel chromatography (30%ethyl acetate/hexanes) of the concentrate afforded the title compound.Yield=900/o colorless oil: MS (ESI+), 462 (M+H).

The following carbamates were prepared as described in the previousexample.

EXAMPLE 5594-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[3-[[N′-[3-(1H-imidazol-1-yl)propylamino]carbonyl]oxy]-(R)-1-methylpropyl]benzenesulfonamide

Yield=70% colorless oil: MS (ESI+), 556 (M+H).

EXAMPLE 5604-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[3-[[N′-[2-(1H-imidazol-1-yl)ethylamino]carbonyl]oxy]-(R)-1-methylpropyl]benzenesulfonamide

Yield=75% colorless oil: MS (ESI+), 542 (M+H).

EXAMPLE 5614-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[[N′-[2-(1H-imidazol-1-yl)ethylamino]carbonyl]oxy]-(R)-1-methylbutyl]benzenesulfonamide

Yield=70% colorless oil: MS (ESI+), 556 (M+H).

EXAMPLE 5624-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl)]-N-[4-[[N′-[3-(1H-imidazol-1-yl)propylamino]carbonyl]oxy]-(R)-1-methylbutyl]benzenesulfonamide

Yield=75% colorless oil: MS (ESI+), 570 (M+H).

EXAMPLE 5634-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[2-[[[N′-[3-(1H-imidazol-1-yl)propyl]-N′-ethylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=70% colorless oil: MS (ESI−), 567 (M−H).

EXAMPLE 5644-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[[[pyrrolidin-1-yl]carbonyl]oxy]-(R)-1-methylbutyl]benzenesulfonamide

Yield=70% colorless oil: MS (ESI+), 516 (M+H).

EXAMPLE 5654-Chloro-N-[5-chloro-2-(hydroxymethyl)phenyl]-N-[4-[[N′-[2-(hydroxyethyl)-N′-methylamino]carbonyl]oxy]-(R)-1-methylbutyl]benzenesulfonamide

Yield=65% colorless oil: MS (ESI+), 520 (M+H).

EXAMPLE 5664-Chloro-N-(2-fluoro-5-chlorophenyl)-N-[2-[[N′-[3-(1H-tetrazol-1-yl)propylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=76% colorless oil: MS (ESI+), 532 (M+H).

EXAMPLE 5674-Chloro-N-(2-fluoro-5-chlorophenyl)-N-[2-[[N′-[3-(1H-tetrazol-2-yl)propylamino]carbonyl]oxy]-(R)-1-methylethyl]benzenesulfonamide

Yield=70% colorless oil: MS (ESI+), 532 (M+H).

EXAMPLE 5684-Chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamide

To a stirred solution of4-chloro-N-(5-chloro-2-fluorophenyl)sulfoanilide (10 g, 31.23 mmol),triphenylphosphine (12.5 g, 45.99 mmol), and ethyl-(s)-lactate (5.43 g,45.99 mmol) in THF (300 mL) was added diethylazodicarboxylate (11.94,68.62 mmol) dropwise at 0° C. under nitrogen. The reaction mixture wasallowed to warm to room temp and stirred for 18 h. and further dilutedwith ethyl acetate (1 L) and washed with water (2×500 mL), brine (1×500mL) and dried over MgSO₄. Filtration and concentration in vacuo,followed by silica gel chromatography (5% ethyl acetate/hexane) of theconcentrate produced the4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(ethoxycarbonyl)]ethyl]-benzenesulfonamidecompound, in 80% yield (10.5 g).

To the solution of above ester (2 g, 4.76 mmol) in THF:MeOH:H₂O/50:20:5was added Lithium hydroxide (0.29 g, 7.14 mmol) and further stirred thereaction mixture for 2 h. The reaction mixture was diluted with 1N HCl(100 mL) and then extracted with ethyl acetate (2×150 mL). The organiclayer was washed with brine and dried over MgSO₄, filtered, andconcentrated to give4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-(carboxyethyl)]benzenesulfonamideas white solid in 75% yield (1.4 g). ¹H NMR (DMSO) 7.92-7.29 (m, 7H),4.60-4.58 (d, 1H), 4.04-4.01 (q, 1H), 1.11-1.09 (d, 2H), MS (ESI+)391.87 (M+H)⁺. Further, the resulting carboxylic acid (1.3 g, 3.31 mmoL)was dissolved in CH₂Cl₂ (50 mL) and DMF (0.3 mL) and oxalyl chloride(0.34 mL, 3.97 mmoL) was added to it. The resulting reaction mixture wasstirred at rt for 1 h. It was then concentrated under reduced pressureto provide the title compound in 95% yield.

EXAMPLE 5694-Chloro-N-5-chloro-2-fluorophenyl)-N-[(1R)-1-[(butylamino)carbonyl]ethyl]benzenesulfonamide

To the solution of N-butylamine (5.5 mg, 0.075 mmol) in 1,2dichloroethane (0.75 mL) in a minireactors was added 2% cross linkedpoly(4-vinyl pyridine) (12.00 ng, 0.105 mmol) resin and solution (0.1 M)of 4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(R)-1chlorocarbonyl)]ethyl]benzenesulfonamide (12.30 mg, 0.030 mmol) in 1,2dichloromethane. The mini reactor was stirred on the shaker for 12 h,followed by quenching the reaction mixture with SCX (92 mg, 0.06 mmol)resin and further stirred on the shaker for additional 18 h. Filteredoff the resin and washed the resin 1,2 dichloroethane (2×0.2 mL) andcombined solvent was collected in microtube and evaporated and theproduct was analyzed by HPLC using the column YMC S7 C18 (3.0×50 mm)with a flow rate of 5.0 mL/min and gradient time of 2.0 min., using thesolvent composition of 10% MeOH —90% H₂O—0.1% TFA, 90% MeOH—10% H₂O—0.1%TFA. The title compound was obtained with 77% purity in 54% yield; MS(ESI) 446.98 (M+H); R_(f) =1.87.

EXAMPLE 5704-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[2-(4-morpholinyl)ethyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner described herein, the title compound was prepared by thereaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 4-(2-aminoethyl)morpholine (25% yield); MS (ES) 503.99 (M+H); R_(f)1.70.

EXAMPLE 5714-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(3,3-diphenylpropyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner described herein, the title compound was prepared by thereaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 3,3-diphenylpropylamine (94% yield); MS (ESI) 584.96 (M+H);R_(f)2.1.

EXAMPLE 5724-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(cyclopropylmethyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner described herein, the title compound was prepared by thereaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith (aminomethyl)cyclopropane (47% yield); MS ESI) 444.95 (M+H); R_(f)1.80.

EXAMPLE 5734-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[2-(4-pyridinyl)ethyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 4-(2-aminoethyl)pyridine (30% yield) MS (ESI) 495.92 (M+H); R_(f)1.49.

EXAMPLE 5744-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[2-(2,4-dichlorophenylethyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2,4-dichlorophenethylamine. (>95% yield); MS (ESI) 562.84 (M+H);R_(f) 2.12.

EXAMPLE 5754-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(adamantylmethyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 1-adamantanemethylamine (>95% yield); MS (ESI) 538.98 (M+H); R_(f)2.17.

EXAMPLE 5764-Chloro-N-5-chloro-2-fluorophenyl)-N-[(1R)-1-[(cyclopentylamino)carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith cyclopentylamine (61% yield) MS (ESI) 458.98 (M+H); R_(f) 1.88.

EXAMPLE 5774-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[(cyclohexylamino)carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-chlorocarbonyl)]ethyl]benzenesulfonamidewith cyclohexylamine (>95% yield); MS (ESI) 473.00 (M+H); R_(f) 1.95.

EXAMPLE 5784-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(1,2,3,4-tetrahydro-1-naphthalenyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamide1,2,3,4-tetrahydro-1-naphthylamine (>95% yield); MS (ESI) 520.96 (M+H);R_(f) 2.02.

EXAMPLE 5794-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(2,3-dihydro-1H-indenyl)amino]carbonylethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2-aminoindan (86% yield); MS (ESI) 506.96 (M+H); R_(f) 1.97.

EXAMPLE 5804-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(1H-indazol-5-yl)amino]carbonylethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 5-aminoindazole (97% yield); MS (ESI) 506.95 (M+H); R_(f) 1.74.

EXAMPLE 5814-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[4-(N,N-diethylamino)-1-methylbutyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2-amino-5-diethylaminopentane (<95% yield); MS (ESI) 532.03 (M+H);R_(f) 1.58.

EXAMPLE 5824-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[(4-pyridinyl)methyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 4-(aminomethyl)pyridine (28% yield);MS (ESI) 481.93 (M+H); R_(f)1.69.

EXAMPLE 5834-Chloro-N-(chloro-2-fluorophenyl)-N-[(1R)-1-[[[(2,6-dichlorophenyl)ethyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2,6-dichlorophenethylamine (94% yield); MS (ESI) 562.98 (M+H);R_(f) 2.04.

EXAMPLE 5844-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[2-[N-ethyl-N-(3-methylphenyl)amino]ethyl]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-chlorocarbonyl)]ethyl]benzenesulfonamidewith N-(2-aminoethyl)-N-ethyl-M-toluidine (<95% yield); MS (ESI) 551.99(M+H); R_(f) 1.72.

EXAMPLE 5854-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(4-tert-butylcyclohexyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 4-tert-butylcyclohexylamine (>95% yield); MS (ESI) 529.03 (M+H);R_(f) 2.20.

EXAMPLE 5864-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[2-(2-thienyl)ethyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2-thiopheneethylamine (>95% yield); MS (ESI) 500.91 (M+H); R_(f)1.90.

EXAMPLE 5874-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(2-phenoxyethyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2-phenoxyethylamine (>95% yield); MS (ESI) 510.95 (M+H); R_(f)1.92.

EXAMPLE 5884-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[(1,3-benzodioxol-5-yl)methyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 3,4-methylenedioxybenzylamine (>95% yield); MS (ESI) 524.93 (M+H);R_(f) 1.84.

EXAMPLE 5894-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(3-ethoxypropyl)amino]carbonyl]ethyl]benzenesulfonamid

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 3-ethoxypropylamine (>95% yield); MS (ESI) 476.99 (M+H); R_(f)1.79.

EXAMPLE 5904-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[(2-tetrahydrofuranyl)methyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith tetrahydrofurfurylamine (93% yield); MS (ESI) 474.99 (M+H); R_(f)1.75.

EXAMPLE 5914-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[3-(4-morpholinyl)propyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)—(chlorocarbonyl)]ethyl]benzenesulfonamidewith 4-(3-aminopropyl)morpholine (44% yield); MS (ESI) 518.00 (M+H);R_(f) 1.51.

EXAMPLE 5924-Chloro-N-5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[[(2R)-6,7-dimethylbicyclo]3.1.1]heptan-2-yl]methyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-chlorocarbonyl)]ethyl]benzenesulfonamidewith (−)-cis-myrtanylamine (>95% yield); MS (ESI) 527.01 (M+H); R_(f),2.14.

EXAMPLE 5934-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(4-phenylbutyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 4-phenylbutylamine (>95% yield); MS (ESI) 522.98 (M+H); R_(f) 2.03.

EXAMPLE 5944-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[2-(4-methylphenyl)ethylamino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2-(p-tolyl)ethylamine (69% yield); MS (ESI) 508.95 (M+H); R_(f)2.01.

EXAMPLE 5954-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[2-(4-flurophenyl)ethyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 4-fluorophenethylamine (68% yield); MS (ESI) 512.94 (M+H); R_(f)1.94.

EXAMPLE 5964-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(2,6-difluorophenylmethyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2,6-difluorobenzylamine (75% yield); MS (ESI) 516.93 (M+H); R_(f)1.86.

EXAMPLE 5974-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(3-hydroxy-2,2-dimethylpropyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith neopentanolamine (73% yield); MS (ESI) 476.99 (M+H); R_(f) 1.74.

EXAMPLE 5984-Chloro-N-(5-chloro-2-fluorophenyl-N-[(1R)-1-[[N-(2-aminoethyl)-N-phenylamino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-5-chloro-2-fluorophenyl)-N-[[(1R)-1-chlorocarbonyl)]ethyl]benzenesulfonamidewith N-phenylethylenediamine (>95% yield); MS (ESI) 509.97 (M+H); R_(f)1.72.

EXAMPLE 5994-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(3-iodophenylmethyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 3-iodobezylamine (>95% yield); MS (ESI) 606.78 (M+H); R_(f) 2.01.

EXAMPLE 6004-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[2-(4-hydroxyphenyl)ethyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith tyramine (44% yield); MS (ESI) 510.94 (M+H); R_(f) 1.73.

EXAMPLE 6014-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[(3-pyridinyl)methyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 3-(aminomethyl)pyridine (15% yield); MS (ESI) 481.95 (M+H); R_(f)1.49.

EXAMPLE 6024-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[(3-(N,N-dibutylamino)propyl]amino]carbonyl]ethyl]Benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 3-(dibutylamino)propylamine (>95% yield); MS (ESI) 560.04 (M+H);R_(f) 1.74.

EXAMPLE 6034-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(3,4-difluorophenylmethyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 3,4-difluorobenzylamine (>95% yield); MS (ESI) 516.93 (M+H); R_(f)1.91.

EXAMPLE 6044-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(5-hydroxy-1,5-dimethylhexyl)amino]carbonyl]ethyl]benezenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith heptaminol hydrochloride (22% yield); MS (ESI) 519.01 (M+H); R_(f)1.69.

EXAMPLE 6054-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(5-chloro-2-hydroxyphenyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2-amino-4-chlorophenol (50% yield); MS (ESI) 516.87 (M+H); R_(f)1.93.

EXAMPLE 6064-Chloro-N-5-chloro-2-fluorophenyl)-N-[(1R)-1-[(tetradecylamino)carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 1-tetradecylamine (38% yield); MS (ESI) 587.07 (M+H); R_(f) 2.73.

EXAMPLE 6074-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(trans-4hydroycyclohexyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith trans-4-aminocyclohexanol hydrochloride (29% yield); MS (ESI)488.99 (M+H); R_(f) 1.69.

EXAMPLE 6084-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[2-(2-pyridinyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-chlorocarbonyl)]ethyl]benzenesulfonamidewith 2-(2-aminoethyl)pyridine (>95% yield); MS (ESI) 495.96 (M+H); R_(f)1.69.

EXAMPLE 6094-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[3-(2-methyl-1-piperidinyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl-N-[[(1R)-1-(chlorocarbonyl)ethyl]benzenesulfonamidewith 1-(3-aminopropyl)-2-pipecoline (>95% yield); MS (ESI) 529.98 (M+H);R_(f) 1.68.

EXAMPLE 6104-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[(2-pyridinyl)methylamino]carbonyl]ethyl]benzenesulfonamid

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2-(aminomethyl)pyridine (>95% yield); MS (ESI) 482.04 (M+H); R_(f)1.69.

EXAMPLE 6114-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(4-methylcyclohexyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 4-methylcyclohexylamine (>95% yield); MS (ESI) 487.00 (M+H); R_(f)2.01.

EXAMPLE 6124-Chloro-N-(5-chloro-2-fluorophenyl)-N-1-[[[(1R)-1-(hydroxymethyl)-2-[(phenylmethyl)thio]-ethyl]amino]carbonyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith S-benzyl-L-cysteinol (75% yield); MS (ESI) 570.93 (M+H); R_(f)1.95.

EXAMPLE 6134-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(2-hydroxy-1,1-dimethylethyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2-amino-2-methyl-1-propanol (58% yield); MS (ESI) 462.96 (M+H);R_(f) 1.71.

EXAMPLE 6144-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[(cycloheptylamino)]carbonyl]ethyl]Benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith cycloheptylamine (83% yield); MS (ESI) 487.00 (M+H); R_(f) 2.00.

EXAMPLE 6154-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(4-oxapentyl)amino]carbonyl]ethyl]benezenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 3-methoxypropylamine (96% yield); MS (ESI) 462.97 (M+H); R_(f)1.73.

EXAMPLE 6164-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(3-methylcyclohexyl)amino]carbonyl]ethyl]benezenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 3-methylcyclohexylamine (76% yield); MS (ESI) 487.01 (M+H); R_(f)2.01.

EXAMPLE 6174-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[4-[2,4-bis(1,1-dimethylpropyl)-phenoxy]butyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 4-(2,4-di-tert-amylphenoxy)butylamine (94% yield); MS (ESI) 679.1(M+H); R_(f) 2.60.

EXAMPLE 6184-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[1-(hyroxymethyl)-2-methylpropyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-chlorocarbonyl)]ethyl]benzenesulfonamidewith DL-valinol (66% yield); MS (ESI) 477.00 (M+H); R_(f) 1.77.

EXAMPLE 6194-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(6-hydroxyhexyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 6-amino-1-hexanol (39% yield); MS (ESI) 490.98 (M+H); R_(f) 1.72.

EXAMPLE 6204-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(1R)-(1-cyclohexylethyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith (R)-(−)-1-cyclohexylethylamine (76% yield); MS (ESI) 501.00 (M+H);R_(f) 2.07.

EXAMPLE 6214-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[(2-(piperidinyl)ethyl]amino]carbonyl)ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 1-(2-aminoethyl)piperidine (20% yield); MS (ESI) 502.05 (M+H);R_(f) 1.69.

EXAMPLE 6224-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[2-(4-methoxyphenyl)ethyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 4-methoxyphenethylamine (64% yield); MS (ESI) 524.97 (M+H); R_(f)1.91.

EXAMPLE 6234-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[N-(2-aminoethyl)-N-(5-nitro-2-pyridinyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2-(2-aminoethylamino)-5-nitropyridine (>95% yield); MS (ESI) 555.93(M+H); R_(f) 1.80.

EXAMPLE 6244-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[(1S)-2-hydroxy-1-(phenylmethyl)ethyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith L-phenylalaninol (75% yield); MS (ESI) 524.96 (M+H); R_(f) 1.87.

EXAMPLE 6254-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(2,5-difluorophenylmethyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2,5-difluorobenzylamine (93% yield); MS (ESI) 516.93 (M+H); R_(f)1.88.

EXAMPLE 6264-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-[[[(2-thienyl)methyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2-aminomethylthiophene (67% yield); MS (ESI) 486.91 (M+H); R_(f)1.84.

EXAMPLE 6274-Chloro-N-(5-chloro-2-fluorophenyl)-N-(1R)-1-[[(2R)-bicyclo[2.2.1]hept-2-yl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith exo-2-aminononobomane (77% yield); MS (ESI) 485.00 (M+H); R_(f)1.96.

EXAMPLE 6284-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[(2-fluorophenyl)ethyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2-fluorophenethylamine (80% yield); MS (ESI) 512.94 (M+H); R_(f)1.93.

EXAMPLE 6294-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(4-hydroxybutyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 4-amino-1-butanol (24% yield); MS (ESI) 462.97 (M+H); R_(f) 1.63.

EXAMPLE 6304-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(4-methoxyphenylmethyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 4-methoxybenzylamine (60% yield); MS (ESI) 510.95 M+H); R_(f) 1.86.

EXAMPLE 6314-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(3,4,5-trimethoxyphenylmethyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 3,4,5-trimethoxybenzylamine (94% yield); MS (ESI) 570.95 M+H);R_(f) 1.80.

EXAMPLE 6324-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[2-[[2-(hydromethyl)phenyl]thio]-phenylmethyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2-(2-(aminomethyl)phenylthio)benzylalcohol (>95% yield); MS (ESI)618.95 (M+H); R_(f) 1.97.

EXAMPLE 6334-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[(2,6-dimethoxyphenylmethyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 2,6-dimethoxybenzylamine (>95% yield); MS (ESI) 540.96 (M+H); R_(f)1.95.

EXAMPLE 6344-Chloro-N-5-chloro-2-fluorophenyl)-N-[(1R)-[[(3,5-dichorophenylmethyl)amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-(chlorocarbonyl)]ethyl]benzenesulfonamidewith 3,5-dichlorobenzylamine (65% yield); MS (ESI) 548.81 (M+H); R_(f)2.07.

EXAMPLE 6354-Chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-[[[4-(1,2,3-thiadiazol-4-yl)phenylmethyl]amino]carbonyl]ethyl]benzenesulfonamide

In a manner similar to previous examples, the title compound wasprepared by the reaction of4-chloro-N-(5-chloro-2-fluorophenyl)-N-[[(1R)-1-chlorocarbonyl)]ethyl]benzenesulfonamidewith R4-(1,2,3-thiadiazol-4-yl)benzylamine (84% yield); MS (ESI) 564.91(M+H); R_(f) 1.82.

EXAMPLE 636 In Vitro Cell-Based Assay of Inhibitors of Amyloid βProduction

Transfected H4 (human neuroglioma) cells stably expressing APPconstructs are used to identify and assess inhibitors of Aβ production.In brief, cells lines are exposed to compounds, and the effect of eachcompound on amyloid β production is determined by measuring the amountof amyloid β produced using an enzyme linked immunosorbent assay (ELISA)that detects amyloid β (see, for example, Seubert et al., (1992) Nature,359:325-327).

Transfected cells that stably express wild-type and variant forms of APPare plated in 96-well format plates at a density sufficient for therapid detection of the secreted amyloid β (experimentally predeterminedfor a particular stable cell population). Cells are plated at least sixhours prior to the introduction of the test compound at which time thegrowth medium is replaced by fresh medium containing the compound to betested. All synthetic agents are initially screened at doses rangingfrom 10-100 μM. Higher dilutions of agents can be used to minimizecytotoxicity. Incubation of cells with a test compound continues forapproximately 16 hours at which time aliquots of medium from each wellare removed and assayed for amyloid β.

ELISA is carried out by methods known in the art (see, e.g., Haass etal., Antibodies: A Laboratory Manual, Harlow and lane, Editors, ColdSpring Harbor Press, 1988) The capture antibody is typically a mousemonoclonal (IgG1/kβ-APPa) which recognizes the carboxyl terminal epitopeof amyloid β. The specificity of the capture antibody insuresmeasurement of amyloid β without interference from other secreted APPfragments that share amino acid sequence (amyloid β 1-16) homology withamyloid β but lack the carboxy-terminal region. The detecting antibodyis typically an affinity-purified rabbit polyclonal antibody that isspecific for the amino terminus of amyloid β.

Results from test compounds are compared to results obtained when cellsare treated with control agents. Amyloid β levels are determined bycomparison to a standard curve obtained by subjecting a range of knownamounts of amyloid β to the ELISA.

A compound is identified as “active” when it inhibits cellularproduction of amyloid β relative to levels in control samples by atleast 50% at the initial tested concentration without significantcytotoxicity. Active compounds are then assayed in dose-responseexperiments to determine the lowest dose of compound necessary forinhibition of amyloid β production. The results obtained when inventioncompounds are subjected to the above described assay results aresummarized in Table B. In the table, an inhibitory concentration (IC₅₀)of less than or equal to 25 nM is represented by +++++; 50 nM≧IC₅₀>25nM, by ++++; 100 nM≧IC₅₀>50 nM, by +++; 500 nM≧IC₅₀>100 nM by ++;IC₅₀>500 nM is represented by +. Compounds which did not displaymeasurable activity in this assay are represented by −.

NUMBER ACTIVITY COMPOUND 1 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[4-(1,1-dioxido-4-thiomorpholinyl)-4-oxo-butyl]-4-fluorophenyl}ethyl)benzene- sulfonamide 2 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[4-(1,1-dioxido-4-thiomorpholinyl)-4-oxo-butyl]-4-fluorophenyl}ethyl)benzene- sulfonamide 3 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-oxo-4-(4-thiomorpholinyl)butyl]-phenyl}ethyl)benzenesulfonamide 4 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(4-methyl-1-piperazinyl)-3-oxo-propyl]phenyl}ethyl)benzenesulfonamide hydrochloride 5 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-oxo-3-(4-thiomorpholinyl)propyl]-phenyl}ethyl)benzenesulfonamide 6 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(1-piperidinyl)propyl]phenyl}- ethyl)benzenesulfonamide 7+++++ 4-chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)- benzenesulfonamide 8 +++++4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 9 +++++4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 10 +++++4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 11 +++++4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 12 +++++methyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-{[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl]- sulfonyl}propanoate 13 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1-piperidinyl)propyl]phenyl}ethyl)- benzenesulfonamide hydrochloride14 +++++ ethyl 4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]- butanoate 15 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(4-methyl-1-piperazinyl)-3-oxo-propyl]phenyl}ethyl)benzenesulfonamide 16 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(2H-tetraazol-2-yl)propyl]phenyl}- ethyl)benzenesulfonamide17 +++++ 4-[2-((1R)-1-{5-chloro[(4-chlorophenyl)-sulfonyl]-2-fluoroanilino}ethyl)-5-fluoro- phenyl]butanoic acid 18 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[2-(3-pyridinylmethoxy)ethyl]phenyl}- ethyl)benzenesulfonamidehydrochloride 19 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(4-fluoro-2-{4-[(methylamino)sulfonyl]butyl}-phenyl)ethyl]benzenesulfonamide 20 +++++4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(4-fluoro-2-{4-[(methylamino)sulfonyl]butyl}-phenyl)ethyl]benzenesulfonamide 21 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(methylsulfonyl)propyl]phenyl}- ethyl)benzenesulfonamide 22+++++ 4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(4-fluoro-2-{4-[(methylamino)sulfonyl]butyl}-phenyl)ethyl]benzenesulfonamide 23 +++++4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]butanoic acid 24 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(1-piperidinyl)butyl]phenyl}- ethyl)benzenesulfonamidehydrochloride 25 +++++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 4-thiomorpholine- carboxylate 26 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(ethylsulfonyl)propyl]-4-fluorophenyl}- ethyl)benzenesulfonamide 27+++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(ethylsulfonyl)propyl]-4-fluorophenyl}- ethyl)benzenesulfonamide 28+++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-(4-methyl-1-piperazinyl)-4-oxo-butyl]phenyl}ethyl)benzenesulfonamide hydro- chloride 29 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[2-(4-pyridinylmethoxy)ethyl]- phenyl}ethyl)benzenesulfonamidehydro- chloride 30 +++++ 5-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]- pentanoic acid 31 +++++4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)-propyl]phenyl}ethyl)benzenesulfonamide 32 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(1H-1,2,4-triazol-1-yl)propyl]-phenyl}ethyl)benzenesulfonamide 33 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-(1H-imidazol-1-yl)butyl]phenyl}- ethyl)benzenesulfonamidehydrochloride 34 +++++ 4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]butanoic acid 35 +++++4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(4-fluoro-2-{3-[(methylamino)sulfonyl]propyl}-phenyl)ethyl]benzenesulfonamide 36 +++++ methyl(2R)-2-[(tert-butoxycarbonyl)amino]-3-{(2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5difluoroanilino}ethyl)-5-fluorobenzyl]- sulfanyl}propanoate 37 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-oxo-4-(1-piperidinyl)butyl]- phenyl}ethyl)benzenesulfonamide38 +++++ 3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]- propanoic acid 39 +++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]- propanoic acid 40 +++++N-(tert-butoxy)-4-[2-((1R)-1-{[(4-chloro-phenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5- fluorophenyl]butanamide41 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)- benzenesulfonamidehydrochloride 42 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)- benzenesulfonamidehydrochloride 43 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)- benzenesulfonamidehydrochloride 44 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)- benzenesulfonamidehydrochloride 45 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-(methylsulfonyl)butyl]phenyl}- ethyl)benzenesulfonamide 46+++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-(methylsulfonyl)butyl]phenyl}- ethyl)benzenesulfonamide 47+++++ 4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(2-{3-[(dimethylamino)sulfonyl]propyl}-4-fluorophenyl)ethyl]benzenesulfonamide 48 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-(1-piperidinyl)butyl]phenyl}- ethyl)benzenesulfonamidehydrochloride 49 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(4H-1,2,4-triazol-4-yl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 50 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(2-{3-[(ethylamino)sulfonyl]propyl}-4-fluoro-phenyl)ethyl]benzenesulfonamide 51 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(1H-tetraazol-1-yl)propyl]phenyl}- ethyl)benzenesulfonamide52 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[(ethylsulfonyl)methyl]-4-fluorophenyl}- ethyl)benzenesulfonamide 53+++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(1H-imidazol-1-yl)propyl]phenyl}- ethyl)benzenesulfonamidehydrochloride 54 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(1H-imidazol-1-yl)propyl]phenyl}- ethyl)benzenesulfonamidehydrochloride 55 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(1H-imidazol-1-yl)propyl]phenyl}- ethyl)benzenesulfonamidehydrochloride 56 +++++ 4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N- methoxybutanamide 57 +++++N-(3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- N,2,2-trimethylpropanamide 58+++++ 4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[4-fluoro-2-(3-hydroxybutyl)phenyl]ethyl}- benzenesulfonamide 59 +++++4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(2-{4-[(ethylamino)sulfonyl]butyl}-4-fluoro-phenyl)ethyl]benzenesulfonamide 60 +++++4-chloro-N-(2,5-difluorophenyl)-N-(1-{4-fluoro-2-[3-(1H-imidazol-1-yl)propyl]phenyl}- ethyl)benzenesulfonamidehydrochloride 61 +++++ N-{4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-2- methoxy-N-methylacetamide 62+++++ methyl 3-{[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluoro-benzyl]sulfonyl}propanoate 63 +++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 4-thio- morpholinecarboxylate 64+++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(ethylsulfanyl)propyl]-4-fluorophenyl}- ethyl)benzenesulfonamide 65+++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[4-(ethylsulfonyl)butyl]-4-fluorophenyl}- ethyl)benzenesulfonamide 66+++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[4-(ethylsulfonyl)butyl]-4-fluorophenyl}- ethyl)benzenesulfonamide 67+++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}- ethyl)benzenesulfonamidehydrochloride 68 +++++ 4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]butanoic acid 69 +++++4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[4-fluoro-2-(4-hydroxypentyl)phenyl]ethyl}- benzenesulfonamide 70 +++++methyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-({3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]propyl}- sulfanyl)propanoate 71+++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-tetraazol-1-yl)propoxy]phenyl}- ethyl)benzenesulfonamide 72 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}- ethyl)benzenesulfonamidehydrobromide 73 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-oxo-3-(1-piperidinyl)-propyl]phenyl}ethyl)benzenesulfonamide 74 +++++4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]- N-methoxy-N-methylbutanamide75 +++++ methyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-({3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]- propyl}sulfonyl)propanoate76 +++++ 4-chloro-N-(2,5-dichlorophenyl)-N-{2-[3-(1-oxido-1-piperidinyl)propoxy]benzyl}- benzenesulfonamide 77 +++++4-chloro-N-(2,5-dichlorophenyl)-N-{2-[3-(1-oxido-1-piperidinyl)propoxy]benzyl}- benzenesulfonamide 78 +++++4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-oxido-1-piperidinyl)propoxy]benzyl}- benzenesulfonamide 79 +++++4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1,1,4-trioxido-4-thiomorpholinyl)propoxy]- benzyl}benzenesulfonamide 80+++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1-piperidinyl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 81 +++++ methyl ({2-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluoro-phenyl]ethyl}sulfinyl)acetate 82 +++++4-chloro-N-(5-chloro-2-fluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}- ethyl)benzenesulfonamidehydrochloride 83 +++++ methyl 3-({2-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluoro-phenyl]ethyl}sulfanyl)propanoate 84 +++++4-bromo-N-(2,5-difluorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 85+++++ 4-chloro-N-{2-[3-(diethylnitroryl)propoxy]-benzyl}-N-(2,5-difluorophenyl)benzene- sulfonamide 86 +++++4-chloro-N-{2-[3-(diethylnitroryl)propoxy]-benzyl}-N-(2,5-difluorophenyl)benzene- sulfonamide 87 +++++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 4-methyl- 1-piperazinecarboxylate88 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(2H-tetraazol-2-yl)propoxy]phenyl}ethyl)- benzenesulfonamide 89 +++++4-chloro-N-(2,5-difluorophenyl)-N-({1-[3-(1-piperidinyl)propoxy]-2-naphthyl}methyl)- benzenesulfonamidehydrochloride 90 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(4-methyl-1H-pyrazol-1-yl)propoxy]- phenyl}ethyl)benzenesulfonamide91 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[2-(2-pyridinylmethoxy)ethyl]- phenyl}ethyl)benzenesulfonamidehydro- chloride 92 +++++ 4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]- N-methylbutanamide 93 +++++N-(allyloxy)-4-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5- fluorophenyl]butanamide 94 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-(4-thiomorpholinylsulfonyl)butyl]-phenyl}ethyl)benzenesulfonamide 95 +++++ methyl({2-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluoro-phenyl]ethyl}sulfanyl)acetate 96 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(methylsulfanyl)propyl]phenyl}- ethyl)benzenesulfonamide 97+++++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 4-thio- morpholinecarboxylate 98+++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-tetraazol-1-yl)propyl]phenyl}ethyl)- benzenesulfonamide 99 +++++4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(4-fluoro-2-{4-[methoxy(methyl)amino]-butyl}phenyl)ethyl]benzenesulfonamide 100 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-tetraazol-1-yl)propyl]phenyl}ethyl)- benzenesulfonamide 101 +++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-[2-(4-morpholinyl)ethyl]propanamide 102 +++++4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[4-fluoro-2-(4-oxopentyl)phenyl]ethyl}- benzenesulfonamide 103 +++++4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[4-fluoro-2-(4-oxobutyl)phenyl]ethyl}- benzenesulfonamide 104 +++++4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N- ethoxybutanamide 105 +++++4-chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)- benzenesulfonamide 106 +++++4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N- ethylbutanamide 107 +++++methyl 3-({2-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluoro-phenyl]ethyl}sulfonyl)propanoate 108 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-oxo-3-(4-thiomorpholinyl)propyl]phenyl}- ethyl)benzenesulfonamide 109+++++ 4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(2-{3-[methyl(methylsulfonyl)amino]propoxy}-phenyl)ethyl]benzenesulfonamide 110 +++++N-{3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N methylnicotinamidehydrochloride 111 +++++ 4-chloro-N-[(1R)-1-(2-{3-[(diethylamino)-sulfonyl]propyl}-4-fluorophenyl)ethyl]-N-(2,5-difluorophenyl)benzenesulfonamide 112 +++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N- isobutylpropanamide 113 +++++methyl 2-amino-3-{[2-((1R)-1-{[(4-chloro-phenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl]sulfonyl}propanoate hydro- chloride 114 +++++4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[4-fluoro-2-(5,5,5-trifluoro-4-oxopentyl)phenyl]- ethyl}benzenesulfonamide115 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(ethylsulfonyl)ethyl]-4-fluorophenyl}- ethyl)benzenesulfonamide 116+++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(4-methyl-1-piperazinyl)propyl]-phenyl}ethyl)benzenesulfonamide 117 +++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-(tetrahydro-2-furanylmethyl)propanamide 118 +++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N- cyclohexylpropanamide 119+++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(2-methyl-1H-imidazol-1-yl)propoxy]- phenyl}ethyl)benzenesulfonamidehydro- chloride 120 +++++ 3-({2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]- ethyl}sulfonyl)propanoicacid 121 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(2,5-dioxo-1-pyrrolidinyl)propoxy]- phenyl}ethyl)benzenesulfonamide122 +++++ 3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl}propyl 4- thiomorpholinecarboxylate 123+++++ tert-butyl 4-{3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]propanoyl}-1-piperazine- carboxylate 124 +++++N-{4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}- N-methylpropanamide 125 +++++4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N- cyclohexylbutanamide 126 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[4-(ethylsulfanyl)butyl]-4-fluorophenyl}- ethyl)benzenesulfonamide 127+++++ 3-{[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl]sulfonyl}- propanoic acid 128+++++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl nicotinate hydrochloride 129+++++ N-[2-(4-chlorophenyl)ethyl]-3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}-ethyl)-5-fluorophenyl]propanamide 130 +++++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N,2,2- trimethylpropanamide 131+++++ methyl ({2-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluoro-phenyl]ethyl}sulfonyl)acetate 132 +++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 4 thiomorpholinecarboxylate133 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(1H-imidazol-1-yl)butyl]phenyl}- ethyl)benzenesulfonamidehydrochloride 134 +++++ 4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N- isobutoxybutanamide 135 +++++1-tert-butyl 4-{2-[2-((1R)-1-{[(4-chloro-phenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5- fluorophenyl]ethyl}1,4-piperazine- dicarboxylate 136 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(4-morpholinyl)-3-oxopropyl]-phenyl}ethyl)benzenesulfonamide 137 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(4-methyl-1-piperazinyl)-3-oxopropyl]-phenyl}ethyl)benzenesulfonamide 138 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[(3E)-3-(hydroxyimino)butyl]phenyl}- ethyl)benzenesulfonamide139 +++++ 4-chloro-N-(2,5-dichlorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 140 +++++4-chloro-N-(2,5-dichlorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide 141 +++++4-chloro-N-(2,5-dichlorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 142 +++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl nicotinate 143 +++++4-[2-((1R)-1-{2,5-dichloro[(4-chlorophenyl)-sulfonyl]anilino}ethyl)-5-fluorophenyl]butanoic acid 144 +++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 4- morpholinecarboxylate 145 +++++4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-N-methyl- butanamide 146 +++++N-benzyl-3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluoro-phenyl]-N-[2-(dimethylamino)ethyl]- propanamide 147 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(2H-tetraazol-2-yl)propyl]phenyl}ethyl)- benzenesulfonamide 148 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[4-(methylsulfanyl)butyl]phenyl}- ethyl)benzenesulfonamide 149+++++ 4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(1R)-1-(4-fluoro-2-{4-[(methylamino)sulfonyl]-butyl}phenyl)ethyl]benzenesulfonamide 150 +++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-[3-(1H-imidazol-1-yl)propyl]propanamide 151 +++++4-chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(1-piperidinyl)propoxy]phenyl}ethyl)benzene- sulfonamide hydrochloride 152+++++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 3 pyridinylmethylcarbamate153 +++++ N-butyl-3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluoro-phenyl]-N-methylpropanamide 154 +++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl isonicotinate 155 +++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-[2-(2-pyridinyl)ethyl]propanamide 156 +++++N-benzyl-3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5- fluorophenyl]propanamide 157+++++ 3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-(3- fluorobenzyl)propanamide158 +++++ methyl (2R)-2-amino-3-({3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- 159 +++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl isonicotinate 160 +++++N-(1,3-benzodioxol-5-ylmethyl)-3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoro-anilino}ethyl)-5-fluorophenyl]propanamide 161 +++++N-(tert-butyl)-3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluoro- phenyl]propanamide 162+++++ 4-chloro-N-(2,5-difluorophenyl)-N-{5-fluoro-2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 163+++++ 4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(4-fluoro-2-{3-[2-(trifluoromethyl)-1H-imidazol-1-yl]propyl}phenyl)ethyl]benzenesulfonamide 164 +++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl-5-fluorophenyl]-N-(2- furylmethyl)propanamide 165+++++ 4-chloro-N-(2,4-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 166 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(2H-tetraazol-2-yl)ethyl]phenyl}ethyl)- benzenesulfonamide 167 +++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-[2-(diethylamino)ethyl]propanamide 168 +++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-(2- pyridinylmethyl)propanamide169 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1S)-1-{2-[3-(1-piperidinyl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 170 +++++ 4-chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 171 +++++ 3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-(4-methylcyclohexyl)propanamide 172 +++++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N,2- dimethylpropanamide 173 +++++4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[4-fluoro-2-(3-oxobutyl)phenyl]ethyl}benzene- sulfonamide 174 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(1H-tetraazol-1-yl)ethyl]phenyl}ethyl)- benzenesulfonamide 175 +++++4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)-propoxy]phenyl}ethyl)benzenesulfonamide 176 +++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(1H-tetraazol-1-yl)ethyl]phenyl}ethyl)- benzenesulfonamide 177 +++++4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-pyrrolidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 178 +++++4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-pyrrolidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 179 +++++4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-phenylethyl]benzenesulfonamide 180 +++++4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-piperidinyl)propyl]benzyl}benzene- sulfonamide hydrochloride 181+++++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2-(4- morpholinyl)ethylcarbamate182 ++++ 4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[4-fluoro-2-(5,5,5-trifluoro-4-hydroxypentyl)-phenyl]ethyl}benzenesulfonamide 183 ++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-[2-(1H-indol-3-yl)ethyl]propanamide 184 ++++N-[1-(2-{4-[(aminocarbonyl)(methyl)amino]-butoxy}phenyl)ethyl]-4-chloro-N-(2,5-difluoro- phenyl)benzenesulfonamide185 ++++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 4-morpholine- carboxylate 186 ++++3-[3-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]propanoic acid 187 ++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-(3- pyridinylmethyl)propanamide188 ++++ 4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-N-methoxy- butanamide 189 ++++ methyl(2S)-2-[(tert-butoxycarbonyl)amino]-3-{[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl]- sulfonyl}propanoate 190 ++++4-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)-5-fluorophenyl]- butanoic acid 191 ++++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methylnicotinamide 192 ++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-(3- pyridinyl)propanamide 193++++ N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- methylpropanamide 194 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 4 morpholinecarboxylate 195++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-3-[3-(1H-imidazol-1-yl)propyl]phenyl}- ethyl)benzenesulfonamidehydrochloride 196 ++++ 4-chloro-N-{(1R)-1-[2-(3-cyanopropyl)-4-fluorophenyl]ethyl}-N-(2,5-difluorophenyl)- benzenesulfonamide 197 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 2-(2- pyridinyl)ethylcarbamate 198++++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 3 pyridinylcarbamate 199++++ 4-chloro-N-(4-fluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 200 ++++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl isonicotinate 201 ++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(4-morpholinyl)-3-oxopropyl]phenyl}ethyl)- benzenesulfonamide 202++++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl nicotinate 203 ++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-(2- methoxyethyl)propanamide204 ++++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 1 piperidinecarboxylate 205++++ 4-[3-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]butanoic acid 206 ++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-(4- fluorobenzyl)propanamide207 ++++ 4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[4-fluoro-2-(5-methyl-4-oxo-5-hexenyl)phenyl]- ethyl}benzenesulfonamide 208++++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2-phenyl- propylcarbamate 209 ++++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyltert-butyl- carbamate 210 ++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-[4-(trifluoromethyl)benzyl]propanamide 211 ++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N,N- diethylpropanamide 212 ++++4-chloro-N-(2,5-difluorophenyl)-N-[1-(2-{3-[[(ethylamino)carbonyl](methyl)amino]-propoxy}phenyl)ethyl]benzenesulfonamide 213 ++++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-2- methoxy-N-methylacetamide 214++++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methylacrylamide 215 ++++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 3-(1H-imidazol-1-yl)propylcarbamate 216 ++++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N- methylnicotinamide 217 ++++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methylacetamide 218 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl isopropylcarbamate 219 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl benzylcarbamate 220 ++++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- methylacetamide 221 ++++4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butanoic acid 222 ++++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- methyl-4-morpholinecarboxamide223 ++++ 4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N,N- diethylbutanamide 224 ++++methyl 4-[{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-propyl}(methyl)amino]-4-oxobutanoate 225 ++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[(1,1-dioxido-4-thiomorpholinyl)methyl]-4-fluorophenyl}ethyl)benzenesulfonamide 226 ++++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyl4-methyl-1- piperazinecarboxylate 227 ++++N,N-diallyl-3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5- fluorophenyl]propanamide 228++++ 3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-(2,2 dimethoxyethyl)propanamide229 ++++ 3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]- N-(2-phenylpropyl)propanamide230 ++++ 4-chloro-N-(2,5-dibromophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 231 ++++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- acetamide 232 ++++4-chloro-N-(2,5-difluorophenyl)-N-{1-[2-(3-{methyl[(methylamino)carbonyl]amino}-propoxy)phenyl]ethyl}benzenesulfonamide 233 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 2 pyridinylmethylcarbamate234 ++++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methylcyclopropanecarboxamide235 ++++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 2(2-pyridinyl)ethylcarbamate 236 ++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-[3-(1H- imidazol-1-yl)propyl]propanamide237 ++++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-oxo-3-(1-piperidinyl)propyl]phenyl}ethyl)- benzenesulfonamide 238++++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- nicotinamide 239 ++++ methyl(2S)-2-{[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)benzyl]- amino}propanoate 240 ++++4-chloro-N-(2,5-difluorophenyl)-N-[(1S)-2-hydroxy-1-methylethyl]benzenesulfonamide 241 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 2(diethylamino)ethylcarbamate 242 ++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-cyclooctyl- propanamide 243 ++++2-[{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}(ethyl)-amino]-1,1-dimethyl-2-oxoethyl acetate 244 ++++N-(2-{3-[(aminocarbonyl)(methyl)amino]-propoxy}benzyl)-4-chloro-N-(2,5-difluoro- phenyl)benzenesulfonamide 245++++ 4-chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(1H-1,2,3-triazol-1-yl)propoxy]phenyl}ethyl)- benzenesulfonamide 246++++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 2,2- dimethoxyethylcarbamate 247 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl diethylcarbamate 248 ++++N-[5-chloro-2-(hydroxymethyl)phenyl]-4-methyl-N-[(1S)-1-methylbutyl]benzene- sulfonamide 249 ++++ tert-butyl4-{3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-propanoyl}-1-piperazinecarboxylate 250 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 4-methyl-1- piperazinecarboxylate 251++++ N-(2,5-difluorophenyl)-4-fluoro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 252 ++++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2- pyridinecarboxylate 253 ++++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-2- methoxy-N-methylacetamide 254++++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 4methyl-1-piperazinecarboxylate 255 ++++N-(tert-butyl)-3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]- propanamide 256 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 3-pyridinyl- methylcarbamate 257 ++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-[2-(4- morpholinyl)ethyl]propanamide 258++++ 4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-N-(3-pyridinyl- methyl)butanamidehydrochloride 259 ++++ N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- ethylacetamide 260 ++++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-2-furamide 261 ++++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methylcyclobutanecarboxamide262 ++++ 4-chloro-N-cyclohexyl-N-{2-[3-(1-piperidinyl)-propoxy]benzyl}benzenesulfonamide hydrochloride 263 ++++4-chloro-N-cyclohexyl-N-{2-[3-(1-piperidinyl)-propoxy]benzyl}benzenesulfonamide hydrochloride 264 ++++4-chloro-N-cyclohexyl-N-{2-[3-(1-piperidinyl)-propoxy]benzyl}benzenesulfonamide hydrochloride 265 ++++4-chloro-N-(2,5-difluorophenyl)-N-[1-(2-{3-[{[(7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methyl]sulfonyl}(methyl)amino]propoxy}-phenyl)ethyl]benzenesulfonamide 266 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl tetrahydro 2- furanylmethylcarbamate267 ++++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl bis(2-methoxyethyl)carbamate268 ++++ 3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-[2-(1H-indol 3-yl)ethyl]propanamide 269++++ 4-chloro-N-(2,5-dichlorophenyl)-N-[(1R)-1-(4-fluoro-2-{4-[(methylamino)sulfonyl]butyl}-phenyl)ethyl]benzenesulfonamide 270 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 2(4-morpholinyl)ethylcarbamate 271 ++++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(4,5-dihydro-1H-imidazol-2-yl)propyl]-4fluorophenyl}ethyl)benzenesulfonamide hydro- chloride 272 ++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)- propanamide 273 ++++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,2- dimethylpropanamide 274 ++++4-tert-butyl-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}benzamide 275 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl bis(2- methoxyethyl)carbamate 276++++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-1-adamantanecarboxamide277 ++++ 4-chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(1H-tetraazol-5-yl)propoxy]phenyl}ethyl)- benzenesulfonamide 278 ++++4-chloro-N-(2,5-difluorophenyl)-N-{1-[2-(4-{ethyl[(methylamino)carbonyl]amino}butoxy)-phenyl]ethyl}benzenesulfonamide 279 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 1benzyl-4-piperidinylcarbamate 280 ++++(2E)-3-[3-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-2-propenoic acid 281 ++++4-chloro-N-(2,5-difluorophenyl)-N-{1-[2-(4-{methyl[(methylamino)carbonyl]amino}-butoxy)phenyl]ethyl}benzenesulfonamide 282 ++++4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[2-(1H-tetraazol-1-ylmethyl)phenyl]ethyl}- benzenesulfonamide 283 ++++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N,3- dimethyl-2-butenamide 284++++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 1-piperidine- carboxylate 285 ++++4-chloro-N-(2-fluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 286 ++++ 4-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenyl]butanoic acid 287 ++++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyltetrahydro-2-furanylmethylcarbamate 288 ++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-(2,5 difluorobenzyl)propanamide289 ++++ N-(4-{[{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-(methyl)amino]sulfonyl}phenyl)acetamide 290 ++++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-[2-(2- pyridinyl)ethyl]propanamide 291++++ N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N-ethyl- 2-methoxyacetamide 292++++ 4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-oxido-1-pyrrolidinyl)propoxy]benzyl}benzene- sulfonamide 293 +++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N,2,2- trimethylpropanamide 294 +++4-chloro-N-(2,5-difluorophenyl)-N-{1-[2-(2-{ethyl[(methylamino)carbonyl]amino}ethoxy)-phenyl]ethyl}benzenesulfonamide 295 +++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 3- pyridinylcarbamate 296 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl benzyl(methyl)carbamate 297+++ N-[1-(2-{3-[[(tert-butylamino)carbonyl]-(methyl)amino]propoxy}phenyl)ethyl]-4-chloro-N-(2,5-difluorophenyl)benzene- sulfonamide 298 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 3(1H-imidazol-1-yl)propylcarbamate 299 +++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methylpropanamide 300 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(2-pyridinyl- methyl)propanamide 301 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]propyl 3-(1H- imidazol-1-yl)propylcarbamate302 +++ 4-chloro-N-{2-[2-(cyclohexylsulfinyl)ethoxy]-benzyl}-N-(2,5-difluorophenyl)benzene- sulfonamide 303 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl diallylcarbamate 304 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-(1- phenylethyl)propanamide 305+++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(2-methyl-1H-imidazol-1-yl)ethyl]phenyl}- ethyl)benzenesulfonamidehydrochloride 306 +++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl1,2,3,4-tetrahydro-1-naphthalenylcarbamate 307 +++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyl2-(4-morpholinyl)- ethylcarbamate 308 +++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methyl-2-(phenylsulfanyl)acetamide 309 +++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3- cyano-N-methylbenzamide 310 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(2,2- dimethoxyethyl)propanamide 311 +++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl cyclo- octylcarbamate 312 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl cyclooctylcarbamate 313 +++4-chloro-N-(2,3-dichlorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 314 +++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-2-thiophenesulfonamide315 +++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl methyl- (phenyl)carbamate 316 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N,N-bis(2-methoxyethyl)propanamide 317 +++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 1,2,3,4-tetrahydro-1-naphthalenylcarbamate 318 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 2-(4- morpholinyl)ethylcarbamate 319+++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methyl-4-morpholinecarboxamide320 +++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,6- dimethoxybenzamide 321 +++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N- methylacetamide 322 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 2(1-methyl-2-pyrrolidinyl)ethylcarbamate 323 +++2-[{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}(methyl)-amino]-1,1-dimethyl-2-oxoethyl acetate 324 +++4-chloro-N-(2,5-dichlorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 325 +++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 2,2- dimethoxyethylcarbamate326 +++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 1,3- benzodioxol-5-ylmethylcarbamate327 +++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methylcyclobutanecarboxamide 328+++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 3 fluorobenzylcarbamate 329+++ 4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-piperidinyl)propyl]benzyl}benzenesulfonamide hydrochloride 330 +++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- ethylpropanamide 331 +++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methylacetamide 332 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 2-(1- pyrrolidinyl)ethylcarbamate 333+++ 3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N- (3,4difluorobenzyl)propanamide 334 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 4 methylcyclohexylcarbamate335 +++ 3-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzoic acid 336 +++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-[2-(1H-1,2,4-triazol-1-ylmethyl)phenyl]ethyl}- benzenesulfonamide 337 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N- methyl-N-phenylpropanamide 338+++ N,N-diallyl-3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]- propanamide 339 +++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(1H-1,2,4-triazol-1-yl)ethyl]phenyl}ethyl)- benzenesulfonamide 340+++ 4-butoxy-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}benzamide 341 +++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N,2,2- trimethylpropanamide 342 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-[4-(trifluoro- methyl)benzyl]propanamide343 +++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 2-(diethyl- amino)ethylcarbamate 344+++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-2-(2-thienyl)acetamide345 +++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 2(1H-indol-3-yl)ethylcarbamate 346 +++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzylmethyl(phenyl)- carbamate 347 +++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methyl-2-nitro-4-(trifluoromethyl)benzene- sulfonamide 348 +++4-chloro-N-(2,5-difluorophenyl)-N-[1-(2-{3-[methyl(phenylsulfonyl)amino]propoxy}- phenyl)ethyl]benzenesulfonamide349 +++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl phenylcarbamate 350 +++2,6-dichloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}benzamide 351 +++methyl 3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl(methyl)- carbamate 352 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N- phenylpropanamide 353 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(tetrahydro-2- furanylmethyl)propanamide354 +++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 3-(1H- imidazol-1-yl)propylcarbamate355 +++ N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl)-N- methylcyclobutanecarboxamide 356+++ 4-chloro-2-[[(4-chlorophenyl)sulfonyl]((1R)-1-{2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)- amino]benzyl acetate 357+++ 4-chloro-N-(2,5-difluorophenyl)-N-{1-[2-(4-{ethyl{(isopropylamino)carbonyl]amino}-butoxy)phenyl}ethyl}benzenesulfonamide 358 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 2,5-difluorobenzylcarbamate359 +++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[(4-pyridinylmethoxy)methyl]phenyl}- ethyl)benzenesulfonamide360 +++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2- (diethylamino)ethylcarbamate361 +++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl methyl- (phenyl)carbamate 362 +++2-chloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}benzamide 363 +++methyl [{4-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-butyl}(methyl)amino](oxo)acetate 364 +++2-[{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}(methyl)-amino]-1,1-dimethyl-2-oxoethyl acetate 365 +++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl cyclo- hexylcarbamate 366 +++2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-N-methoxy- acetamide 377 +++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2- nitrobenzamide 378 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]propyl 1- piperidinecarboxylate 379 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl isopropyl- carbamate 380 +++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[(3-pyridinylmethoxy)methyl]phenyl}- ethyl)benzenesulfonamide381 +++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methyl-2-(2-thienyl)acetamide382 +++ 4-chloro-N-(2,5-difluorophenyl)-N-{1-[2-(2-{methyl[(methylamino)carbonyl]amino}-ethoxy)phenyl]ethyl}benzenesulfonamide 383 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(2,5-difluoro- benzyl)propanamide 384+++ N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N-methyl-2-(phenylsulfanyl)acetamide 385 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 1 phenylethylcarbamate 386+++ N-{3-[2-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-2- methoxy-N-methylacetamide 387+++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N,4,7,7tetramethyl-3-oxo-2-oxabicyclo[2.2.1]heptane- 1-carboxamide 388 +++N-(1,3-benzodioxol-5-ylmethyl)-3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoro-anilino}ethyl)phenyl]propanamide 389 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl benzyl- carbamate 390 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N-(2- phenylethyl)propanamide 391+++ 4-chloro-N-(2-chloro-3-pyridinyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 392 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 2-methoxy- ethylcarbamate 393 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-[2-(1- pyrrolidinyl)ethyl]propanamide394 +++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methylcyclopentanecarboxamide395 +++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2,2- dimethoxyethylcarbamate 396+++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 2 methoxyethylcarbamate 397+++ 4-chloro-N-(2,5-difluorophenyl)-N-[1-(2-{2-[[(dimethylamino)carbonyl](methyl)amino]-ethoxy}phenyl)ethyl]benzenesulfonamide 398 +++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl isobutylcarbamate 399 +++4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(2,5-dioxo-1-pyrrolidinyl)propoxy]benzyl}- benzenesulfonamide 400 +++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[(2-pyridinylmethoxy)methyl]phenyl}- ethyl)benzenesulfonamide401 +++ 3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-cyclohexyl- propanamide 402 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 2-phenyl- propylcarbamate 403 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-phenyl- propanamide 404 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(2-furyl- methyl)propanamide 405 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]- ethanesulfonic acid 406 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)propanamide 407 +++4-chloro-N-{2-[3-(cyclohexylsulfinyl)propoxy]-benzyl}-N-(2,5-difluorophenyl)benzene- sulfonamide 408 +++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,6- difluorobenzamide 409 +++4-butyl-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}benzamide 410 +++4-chloro-N-(2,5-difluorophenyl)-N-{1-[2-(3-{methyl[(4-nitrophenyl)sulfonyl]amino}-propoxy)phenyl]ethyl}benzenesulfonamide 411 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]propyl isopropyl- carbamate 412 +++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N-ethyl- 2,2-dimethylpropanamide413 +++ 4-chloro-N-(2,5-difluorophenyl)-N-[2-(3-hydroxypropyl)benzyl]benzenesulfonamide 414 +++ 1-tert-butyl4-[2-((1R)-1-{[(4-chlorophenyl)- sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl] 1,4-piperazinedicarboxylate 415 +++ methyl[{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- (methyl)amino](oxo)acetate416 +++ [[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl](methyl)amino]- acetic acid hydrochloride417 +++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N-ethyl-2-(phenylsulfanyl)acetamide 418 +++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2-(1-methyl-2-pyrrolidinyl)ethylcarbamate 419 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 4 fluorobenzylcarbamate 420+++ 4-chloro-N-(2,5-difluorophenyl)-N-({3-[3-(1-piperidinyl)propoxy]-2-naphthyl}methyl)- benzenesulfonamidehydrochloride 421 +++ 4-chloro-N-(2,5-difluorophenyl)-N-({3-[3-(1-piperidinyl)propoxy]-2-naphthyl}methyl)- benzenesulfonamidehydrochloride 422 +++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 2 phenylethylcarbamate 423+++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-4- propylbenzamide 424 +++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2- methoxy-N-methylbenzamide 425+++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl benzyl[2-(dimethylamino)ethyl]carbamate 426 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-methyl-N- phenylpropanamide 427 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(2-phenyl- propyl)propanamide 428 +++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3- cyclopentyl-N-methylpropanamide429 +++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl tetrahydro2-furanylmethylcarbamate 430 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(3,4- difluorobenzyl)propanamide 431 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(1-phenyl- ethyl)propanamide 432 +++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- acrylamide 433 +++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N,3- dimethyl-2-butenamide 434 +++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- ethyl-2-methoxyacetamide 435 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 2 furylmethylcarbamate 436+++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 2-(1H- indol-3-yl)ethylcarbamate 437+++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl isopropylcarbamate 438 +++4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[2-(1H-imidazol-1-ylmethyl)phenyl]ethyl}- benzenesulfonamide hydrochloride439 +++ 4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[2-(1H-tetraazol-1-ylmethyl)phenyl]ethyl}- benzenesulfonamide 440 +++4-tert-butyl-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-N-methylbenzamide441 +++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl butyl(methyl)carbamate 442+++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methylcyclopentanecarboxamide443 +++ 3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(2-phenyl- ethyl)propanamide 444 +++N-benzyl-3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluoro-phenyl]-N-methylpropanamide 445 +++4-chloro-N-(2,5-difluorophenyl)-N-{1-[2-(4-{ethyl[(ethylamino)carbonyl]amino}butoxy)-phenyl]ethyl}benzenesulfonamide 446 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(3-pyridinyl- methyl)propanamide 447 +++6-amino-N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}- N-methylhexanamidehydrochloride 448 +++ 6-amino-N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}- N-methylhexanamidehydrochloride 449 +++ N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N-ethyl- cyclobutanecarboxamide 450+++ 4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(2-pyridinylcarbonyl)-2-piperidinyl]ethoxy}- benzyl)benzenesulfonamide 451+++ 4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(3-pyridinylcarbonyl)-2-piperidinyl]ethoxy}- benzyl)benzenesulfonamide 452+++ N-benzyl-3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N- methylpropanamide 453 +++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N-ethyl- acetamide 454 +++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N-ethyl- 2-methylpropanamide 455+++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 1-benzyl- 4-piperidinylcarbamate456 +++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 3- pyridinylcarbamate 457 +++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 2 phenylpropylcarbamate 458+++ N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}- N,2,2-trimethylpropanamide 459+++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl 2(4-chlorophenyl)ethylcarbamate 460 +++4-chloro-N-(2-chlorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 461 +++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N- methylpropanamide 462 +++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methyl-3-nitrobenzenesulfonamide 463 +++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- methylbutanamide 464 +++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2- fluorobenzamide 465 +++4-chloro-N-(2,5-difluorophenyl)-N-({3-[3-(1-piperidinyl)propoxy]-2-pyridinyl}methyl)- benzenesulfonamidehydrochloride 466 +++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methylbenzamide 467 +++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluoro- N-methyloctanamide 468+++ methyl 4-[{2-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-ethyl}(methyl)amino]-4-oxobutanoate 469 +++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl)-N- methyl-2-(2-thienyl)acetamide470 +++ N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- ethylbutanamide 471 +++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-4- ethyl N-methylbenzamide 472 +++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]propyl methyl- (phenyl)carbamate 473 +++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2-(1H- indol-3-yl)ethylcarbamate474 ++ N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- methylcyclopentanecarboxamide475 ++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-2-thiophenecarboxamide476 ++ 4-chloro-N-(2,5-difluorophenyl)-N-[1-(2-{3-[[(4-fluorophenyl)sulfonyl](methyl)amino]-propoxy}phenyl)ethyl]benzenesulfonamide 477 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methyl-1,3-benzodioxole-5-carboxamide 478 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(2-methoxy- ethyl)propanamide 479 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]propyl diethylcarbamate 480 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyl2-(1H-indol-3- yl)ethylcarbamate 481 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 3- pyridinylmethylcarbamate 482 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methyl-2-nitrobenzenesulfonamide 483 ++ methyl{[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)benzyl]- amine}acetate 484 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methylbutanamide 485 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- ethyl-3-methylbutanamide 486 ++1-tert-butyl 4-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluroanilino}ethyl)benzyl] 1,4- piperazinedicarboxylate487 ++ N-[2-(4-chlorophenyl)ethyl]-3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}- ethyl)phenyl]propanamide488 ++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methylbenzamide 489 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N,N- dipropylbutanamide 490 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N,3- dimethylbutanamide 491 ++4-chloro-N-(2,5-difluorophenyl)-N-[2-(1H-tetraazol-1-ylmethyl)benzyl]benzene- sulfonamide 492 ++4-chloro-N-{2-[3-(1,1-dioxido-4-thio-morpholinyl)propoxy]benzyl}-N-phenyl- benzenesulfonamide hydrochloride493 ++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl diallylcarbamate 494 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N-methyl-2-(phenylsulfanyl)acetamide 495 ++(2E)-N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- methyl-2-butenamide 496 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}[1,1′- biphenyl]-4-carboxamide 497++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,3,6- trifluorobenzamide 498 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]propyl benzyl- carbamate 499 ++ ethyl4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butanoate 500 ++N-(sec-butyl)-3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]- propanamide 501 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N,3- dimethyl-2-butenamide 502 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,4- difluoro-N-methylbenzamide503 ++ (2E)-N-(2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methyl-2-butenamide 504 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- ethylpropanamide 505 ++2-bromo-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-N-methylbenzamide506 ++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N-ethyl- 4-morpholinecarboxamide507 ++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2,5- difluorobenzylcarbamate 508++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 2,5- difluorobenzylcarbamate 509 ++1-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyl3-(1H-imidazol-1- yl)propylcarbamate 510 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methyl-1-adamantanecarboxamide511 ++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methylcyclohexanecarboxamide 512++ 3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-[2-(1-methyl2-pyrrolidinyl)ethyl]propanamide 513 ++2-chloro-N-{[2-(1-{[(3-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- N-methylbenzamide 514 ++(2E)-N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- ethyl-2-butenamide 515 ++N-benzyl-3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]- propanamide 516 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-[2- (diethylamino)ethyl]propanamide 517++ N-butyl-2-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]- N-methylpropanamide 518 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,6- dimethoxy-N-methylbenzamide519 ++ 3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(3- fluorobenzyl)propanamide 520 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- 2,5-difluorobenzamide 521 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzylbis(2-methoxy- ethyl)carbamate 522 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N,3- dimethylbutanamide 523 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,3- difluoro-N-methylbenzamide524 ++ 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(2H-tetraazol-2-yl)propyl]phenyl}ethyl)- benzenesulfonamide 525 ++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 3- fluorobenzylcarbamate 526 ++4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[2-(1H-imidazol-1-yl)ethyl]phenyl}ethyl)- benzenesulfonamidehydrochloride 527 ++ methyl 4-({3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-propyl}amino)-4-oxobutanoate 528 ++4-butoxy-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-N-methylbenzamide529 ++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 3-pyridinyl- methylcarbamate 530 ++2-[{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-(methyl)amino]-1,1-dimethyl-2-oxoethyl acetate 531 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(3-pyridinyl)- propanamide 532 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-isobutyl- propanamide 533 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methyl-9-oxo-9H-fluorene-4-carboxamide 534 ++4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[2-(2H-tetraazol-2-ylmethyl)phenyl]ethyl}- benzenesulfonamide 535 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl benzyl[2-(dimethylamino)ethyl]carbamate 536 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,4- difluorobenzamide 537 ++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]ethyl sec-butylcarbamate 538 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2-(2- pyridinyl)ethylcarbamate 539++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 1- phenylethylcarbamate 540 ++4-chloro-N-(2,5-difluorophenyl)-N-[1-(2-{3-[methyl(4-toluidinocarbonyl)amino]propoxy}-phenyl)ethyl]benzenesulfonamide 541 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N-ethyl- 2-(2-thienyl)acetamide 542++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 2-(2-pyridinyl)- ethylcarbamate 543 ++N-[1-(2-{3-[[(4-tert-butylphenyl)sulfonyl]-(methyl)amino]propoxy}phenyl)ethyl]-4-chloro-N-(2,5-difluorophenyl)benzene- sulfonamide 544 ++N-benzyl-3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N- [2(dimethylamino)ethyl]propanamide 545 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-1- naphthamide 546 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]propyl butyl- (methyl)carbamate 547 ++4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(2,3,4,5,6-pentafluorophenyl)ethyl]benzene- sulfonamide 548 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N-ethyl- 3-methyl-2-butenamide 549++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 3,4- difluorobenzylcarbamate 550++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl diethyl- carbamate 551 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N,2- dimethylpropanamide 552 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-(4-fluoro- benzyl)propanamide 553 ++3-chloro-N-(2,5-difluorophenyl)-N-[1-(2-{4-[[(ethylamino)carbonyl](methyl)amino]-butoxy}phenyl)ethyl]benzenesulfonamide 554 ++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl benzyl- (methyl)carbamate 555 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]propyl 3,4- difluorobenzylcarbamate 556 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 1- piperidinecarboxylate 557 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 4-methyl- cyclohexylcarbamate 558++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N,4- dimethyl-2-nitrobenzamide 559++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- ethyl-2-methylpropanamide 560 ++methyl 4-[{2-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-ethyl}(ethyl)amino]-4-oxobutanoate 561 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- methylbenzamide 562 ++ allyl3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl- (methyl)carbamate 563 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyl2,2-dimethoxy- ethylcarbamate 564 ++4-chloro-N-(2,5-difluorophenyl)-N-[1-(2-{2-[methyl(methylsulfonyl)amino]ethoxy}- phenyl)ethyl]benzenesulfonamide565 ++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2-(4- chlorophenyl)ethylcarbamate566 ++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl benzyl- (methyl)carbamate 567 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl benzyl- carbamate 568 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2- pyridinylmethylcarbamate 569 ++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 2- phenylethylcarbamate 570 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-2-nitrobenzamide 571 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3,4- difluoro-N-methylbenzamide572 ++ 4-chloro-N-[1-(2-{2-[[(diethylamino)carbonyl]-(methyl)amino]ethoxy}phenyl)ethyl]-N-(2,5difluorophenyl)benzenesulfonamide 573 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methyl-2-furamide 574 ++(2S)-2-{[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)benzyl]- amino}propanoic acid 575 ++4-chloro-N-(2,5-difluorophenyl)-N-[1(2-{3-[[(4-methoxyphenyl)sulfonyl](methyl)amino]-propoxy}phenyl)ethyl]benzenesulfonamide 576 ++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 4-fluoro- benzylcarbamate 577 ++N-[1-(2-{4-[[(tert-butylamino)carbonyl](ethyl)-amino]butoxy}phenyl)ethyl]-4-chloro-N-(2,5difluorophenyl)benzenesulfonamide 578 ++N-benzyl-4-chloro-N-(2,5-difluorophenyl)- benzenesulfonamide 579 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methyl-2-thiophenecarboxamide580 ++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-4- cyano-N-methylbenzamide 581 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyltetrahydro-2- furanylmethylcarbamate 582 ++2,5-dichloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-propyl}-N-methylbenzenesulfonamide 583 ++2-chloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-propyl}-N-methylbenzenesulfonamide 584 ++4-butyl-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl} N-methylbenzamide585 ++ 4-chloro-N-(2,5-difluorophenyl)-N-[2-(1H-1,2,4-triazol-1-ylmethyl)benzyl]benzene- sulfonamide 586 ++N-[1-(2-{4-[[(tert-butylamino)carbonyl]-(methyl)amino]butoxy}phenyl)ethyl]-4-chloro-N-(2,5-difluorophenyl)benzenesulfonamide 587 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyl2-(1-methyl-2- pyrrolidinyl)ethylcarbamate 588 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- methylpentanamide 589 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- benzamide 590 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2- methylbenzamide 591 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- ethylbenzamide 592 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- ethyl-2-thiophenecarboxamide 593++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 4-(trifluoro- methyl)benzylcarbamate 594 ++4-chloro-N-(2,5-difluorophenyl)-N-{1-[2-(2-{ethyl[(ethylamino)carbonyl]amino}ethoxy)-phenyl]ethyl}benzenesulfonamide 595 ++{[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl]amino}acetic acid hydrochloride 596 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N- methyl-4-morpholinecarboxamide597 ++ 4-chloro-N-(2,5-difluorophenyl)-N-(2-{3-[[(dimethylamino)carbonyl](methyl)amino]-propoxy}benzyl)benzenesulfonamide 598 ++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 2-(4- chlorophenyl)ethylcarbamate 599++ 4-chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(methyl{[4-(trifluoromethyl)phenyl]sulfonyl}-amino)propoxy]phenyl}ethyl)benzene- sulfonamide 600 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- ethylcyclobutanecarboxamide 601++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl diethyl- carbamate 602 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-4-nitrobenzamide 603 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2- cyclohexyl-N-methylacetamide604 ++ 4-chloro-N-{2-[3-(cyclohexylsulfonyl)-propoxy]benzyl}-N-(2,5-difluorophenyl)- benzenesulfonamide 605 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-4- cyano-N-methylbenzamide 606 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-4- cyanobenzamide 607 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3,5- dinitrobenzamide 608 ++N-(2,5-difluorophenyl)-4-methyl-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 609 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- ethylpentanamide 610 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyl2-(1-pyrrolidinyl)- ethylcarbamate 611 ++4-chloro-N-(2,5-difluorophenyl)-N-[6-(1-piperidinyl)hexyl]benzenesulfonamide hydrochloride 612 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzylisobutylcarbamate 613 ++ tert-butyl 6-[{3-[2-({[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]-propyl}(methyl)amino]-6-oxohexylcarbamate 614 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 1,3-benzodioxol-5-ylmethylcarbamate 615 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 4- morpholinecarboxylate 616 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3,5- difluoro-N-methylbenzamide617 ++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N,2,4,6tetramethylbenzenesulfonamide 618 ++ S-methyl4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl- (methyl)thiocarbamate 619 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl-5-fluorobenzyl 4-fluoro- benzylcarbamate 620 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]propyl 4-fluoro- benzylcarbamate 621 ++4-chloro-N-(2,5-difluorophenyl)-N-[2-(3-hydroxy-1-propynyl)benzyl]benzene- sulfonamide 622 ++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl (1S)-1- phenylethylcarbamate 623 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- 2,3,6-trifluoro-N-methylbenzamide624 ++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl butyl- (methyl)carbamate 625 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- ethyl-2-furamide 626 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl diallylcarbamate 627 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}- N-methylcyclohexanecarboxamide628 ++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- N-methyl-2,2-diphenylacetamide629 ++ 4-chloro-N-phenyl-N-{2-[3-(1-piperidinyl)-propyl]benzyl}benzenesulfonamide hydro- chloride 630 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- 2-fluoro-N-methylbenzamide 631 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyldiallyl- carbamate 632 ++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 3-pyridinyl- carbamate 633 ++ S-methyl3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl- (methyl)thiocarbamate 634 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]propyl (1S)-1- phenylethylcarbamate 635 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzylphenylcarbamate 636 ++ 4-chloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-propyl}-N-methyl-2-nitrobenzamide 637 ++N-∴3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2-iodo- N-methylbenzamide 638 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N- methylbutanamide 639 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyl2,5-difluoro- benzylcarbamate 640 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2-phenyl- ethylcarbamate 641 ++2-bromo-N-{3-(2-({[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}methyl)- phenoxy]propyl}-N-methylbenzamide642 ++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy}ethyl}-N- ethyl-3-methyl-2-butenamide 643++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3,4- dimethoxy-N-methylbenzamide644 ++ 2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 1,2,3,4-tetrahydro-1-naphthalenylcarbamate 645 ++4-chloro-N-{2-[3-(4-hydroxy-1-piperidinyl)-propoxy]benzyl}-N-phenylbenzenesulfonamide hydrochloride 646 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}- N-ethylbutanamide 647 ++2,4-dichloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-propyl}-N-methylbenzenesulfonamide 648 ++4-chloro-N-(2,5-difluorophenyl)-N-{2-[2-[1-(4-ethoxybenzoyl)-2-piperidinyl]ethoxy}- benzyl)benzenesulfonamide 649++ (2E)-N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}- N-ethyl-2-butenamide 650 ++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl sec-butyl- carbamate 651 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- 3,4,5-trimethoxybenzamide 652 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-4- methoxy-N-methylbenzamide 653++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-3- cyclopentyl-N-methylpropanamide654 ++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-4- fluoro-N-methylbenzamide 655 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]-N-isopropyl- propanamide 656 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-4-propylbenzamide 657 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methyl-3-(trifluoromethyl)benzamide 658 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 4-(trifluoromethyl)benzylcarbamate 659 ++(2S)-2-[[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)benzyl]- (methyl)amino]propanoicacid hydrochloride 660 ++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 1,2,3,4- tetrahydro-1-naphthalenylcarbamate661 ++ 4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(3-fluorobenzoyl)-2-piperidinyl]ethoxy}benzyl)- benzenesulfonamide 662 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyl2-(diethylamino)- ethylcarbamate 663 ++4-chloro-N-(3-chlorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 664 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methylpentanamide 665 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-2,3- difluoro-N-methylbenzamide666 ++ N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N-methyl-5-(2-oxohexahydro-1H-thieno[3,4-d]- imidazol-4-yl)pentamide 667++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 2-furylmethyl- carbamate 668 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-3,5-dinitrobenzamide 669++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 2-methoxy- ethylcarbamate 670 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- 2,3,4-trifluoro-N-methylbenzamide671 ++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-2-naphthalenesulfonamide672 ++ 4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(2-iodobenzyl)-2-piperidinyl]ethoxy}benzyl)- benzenesulfonamide 673 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyl1,3- benzodioxol-5-ylmethylcarbamate 674 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzylisopropyl- carbamate 675 ++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl cyclohexyl- carbamate 676 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}- 2-ethyl-N-methylhexanamide 677 ++isobutyl 3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl- (methyl)carbamate 678 ++benzyl 3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl- (methyl)carbamate 679 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- 4-fluorobenzamide 680 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}- N,2-dimethylbenzamide 681 ++2-({[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}methyl)phenylacrylate 682 ++ 2,4-dichloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-5-fluorobenzamide683 ++ 4-bromo-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-N-methylbenzamide684 ++ 3-chloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-propyl}-N-methylbenzenesulfonamide 685 ++2-[2-((1R)-1-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]- ethyl cyclohexylcarbamate686 ++ N-{3-[2-(1-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-butyl}-2-cyclohexyl-N-methylacetamide 687 ++N-{3-[2-(1-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-3-methylbenzamide688 ++ 3-chloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-N-methylbenzamide689 ++ 4-chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-nitrophenyl)sulfinyl]propoxy}benzyl)benzene- sulfonamide 690 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3- methoxybenzamide 691 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2- furylmethylcarbamate 692 ++4-chloro-N-(2,5-difluorophenyl)-N-[1-(2-{3-[[(4-iodophenyl)sulfonyl](methyl)amino]-propoxy}phenyl)ethyl]benzenesulfonamide 693 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N,2- dimethylbenzamide 694 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- ethyl-3-methylbutanamide 695 ++4-chloro-N-(2,5-difluorophenyl)-N-[1-(2-{2-[[(isopropylamino)carbonyl](methyl)amino]-ethoxy}phenyl)ethyl]benzenesulfonamide 696 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}- N,3-dimethylbenzamide 697 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N-methyl-2-(trifluoromethyl)benzamide 698 ++4-chloro-N-[1-(2-{2-[[(diethylamino)carbonyl]-(ethyl)amino]ethoxy}phenyl)ethyl]-N-(2,5-difluorophenyl)benzenesulfonamide 699 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3- fluoro-N-methylbenzamide 700 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N,2,4- trimethylpentanamide 701 ++4-chloro-N-(2,5-difluorophenyl)-N-{1-[2-(2-{methyl[(2,2,2-trifluorophenyl)sulfonyl]-amino}ethoxy)phenyl]ethyl}benzene- sulfonamide 702 ++4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(phenylsulfinyl)propoxy]benzyl}benzene- sulfonamide 703 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methyl-4-(trifluoromethyl)benzamide 704 ++4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(2,6-dioxo-1-piperidinyl)propoxy]benzyl}benzene- sulfonamide 705 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N-ethyl- 2-(2-thienyl)acetamide 706++ 4-chloro-N-(2,4-dichlorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 707 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- 4-methylbenzamide 708 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- ethyl-2-furamide 709 ++N-[1-(2-{2-[[(tert-butylamino)carbonyl]-(ethyl)amino]ethoxy}phenyl)ethyl]-4-chloro- N-(2,5difluorophenyl)benzenesulfonamide 710 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- 2,4,5-trifluoro-N-methylbenzamide711 ++ 4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1-piperidinyl)-1-propynyl]benzyl}benzene- sulfonamide hydrochloride 712 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-3- cyclopentyl-N-methylpropanamide713 ++ 2,4,6-trichloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-N-methylbenzamide714 ++ S-methyl 4-[2-(1-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- butyl(ethyl)thiocarbamate715 ++ 2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)benzyl benzyl(methyl)- carbamate 716 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-2- iodo-N-methylbenzamide 717 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N- methylpentamide 718 ++4-chloro-N-phenyl-N-{2-[3-(1-pyrrolidinyl)-propoxy]benzyl}benzenesulfonamide hydro- chloride 719 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-4-iodo- N-methylbenzamide 720 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzylbutyl(methyl)- carbamate 721 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- ethylcyclopentanecarboxamide 722++ 4-chloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-N-methylbenzamide723 ++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3- nitrobenzamide 724 ++N-[1-(2-{2-[[(tert-butylamino)carbonyl]-(methyl)amino]ethoxy}phenyl)ethyl]-4-chloro-N-(2,5-difluorophenyl)benzenesulfonamide 725 ++4-chloro-N-(2,5-difluorophenyl)-N-{1-[2-(2-{ethyl[(isopropylamino)carbonyl]amino}-ethoxy)phenyl]ethyl}benzenesulfonamide 726 ++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl 3,4- difluorobenzylcarbamate 727 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,5- difluoro-N-methylbenzamide728 ++ 2,4,6-trichloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}benzamide 729 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2- methoxyethylcarbamate 730 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]propyl phenylcarbamate 731 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyl2-(4-chloro- phenyl)ethylcarbamate 732 ++(2Z)-N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3- phenyl-2-propenamide 733 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}- 2-fluoro-N-methylbenzamide734 ++ 4-chloro-N-(2,5-difluorophenyl)-N-(2-{3-[[(isopropylamino)carbonyl](methyl)amino]-propoxy}benzyl)benzenesulfonamide 735 ++4-chloro-N-(2,5-difluorophenyl)-N-[1-(2-{2-[(isopropylsulfonyl)(methyl)amino]ethoxy}-phenyl)ethyl]benzenesulfonamide 736 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,5- bis(trifluoromethyl)benzamide737 ++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-3-nitrobenzamide 738 ++(2Z)-N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-Nmethyl-3-phenyl-2-propenamide 739 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- ethylacrylamide 740 ++4-chloro-N-(2,5-dichlorophenyl)-N-{2-[3-(1H-imidazol-1-yl)propoxy]benzyl}benzene- sulfonamide hydrochloride 741 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N,4- dimethylbenzamide 742 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- 2,3,4,5,6-pentafluorobenzamide743 ++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 2-phenyl- ethylcarbamate 744 ++2,2,2-trichloro-N-{2-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- ethyl}-N-ethylacetamide745 ++ N-{2-[2-(1-benzoyl-2-piperidinyl)ethoxy]-benzyl}-4-chloro-N-(2,5-difluorophenyl)benzene- sulfonamide 746 ++4-chloro-N-(2-{2-[1-(3,5-difluorobenzyl)-2-piperidinyl]ethoxy}benzyl)-N-(2,5-difluoro- phenyl)benzenesulfonamide747 ++ N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-4- fluoro-N-methylbenzamide 748++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 4-fluoro- benzylcarbamate 749 ++4-chloro-N-{2-[3-(3,6-dihydro-1(2H)-pyridinyl)-propoxy]benzyl}-N-phenylbenzenesulfonamide hydrochloride 750 ++2,4-dichloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-propyl}-5-fluoro-N-methylbenzamide 751 ++4-chloro-N-(2,5-difluorophenyl)-N-[2-(2H-tetraazol-2-ylmethyl)benzyl]benzene- sulfonamide 752 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N-methyl[1,1′-biphenyl]-4-carboxamide 753 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,4- dimethoxy-N-methylbenzamide754 ++ 4-chloro-N-{2-[2-(cyclohexylfulfonyl)ethoxy]-benzyl}-N-(2,5-difluorophenyl)benzene- sulfonamide 755 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,6- difluoro-N-methylbenzamide756 ++ N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- ethyl-2-thiophenecarboxamide 757++ S-ethyl-3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl- (methyl)thiocarbamate 758 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzylsec- butylcarbamate 759 ++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N-methyl-2-phenylcyclopropanecarboxamide 760 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl bis(2- methoxyethyl)carbamate 761++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl-3- fluorobenzamide 762 ++2-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]ethyl phenylcarbamate 763 ++3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenyl]propyl benzyl(methyl)carbamate 764 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 3- fluorobenzylcarbamate 765 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-4- iodo-N-methylbenzamide 766 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl-N,3- dimethylbenzamide 767 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- ethylbenzamide 768 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl-4- ethoxy-N-methylbenzamide 769 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N-ethyl- 1-adamantanecarboxamide770 ++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methyl-4-(trifluoromethoxy)benzamide 771 ++ S-methyl2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl(ethyl)- thiocarbamate 772 ++4-chloro-N-(2,5-difluorophenyl)-N-[2-(1H-imidazol-1-ylmethyl)benzyl]benzene- sulfonamide 773 ++4-chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(methyl{[(E)-2-phenylethyl]sulfonyl}amino)-propoxy]phenyl}ethyl)benzenesulfonamide 774 ++2-chloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]- propyl}-N-methylbenzamide775 ++ N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-2- methoxy-N-methylbenzamide 776++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-1-naphthalenesulfonamide777 ++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- ethylpentamide 778 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,3,4,5tetrafluoro-N-methylbenzamide 779 ++ methyl(2S)-2-[[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)benzyl]- (methyl)amino]propanoate780 ++ 4-chloro-N-(2,5-difluorophenyl)-N-[2-(2-{1-[(2-phenylcyclopropyl)carbonyl]-2-piperidinyl}ethoxy)benzyl]benzenesulfonamide 781 ++4-chloro-N-(1-methylbutyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 782 ++4-chloro-N-(1-methylbutyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 783 ++(2E)-1-N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N methyl-2-butenamide 784 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,2- diphenylacetamide 785 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-2- cyclohexyl-N-ethylacetamide 786++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3- methoxy-N-methylbenzamide 787++ 4-chloro-N-(2,5-difluorophenyl)-N-[2-(2-{1-[(2-fluorobenzoyl)-2-piperidinyl]ethoxy}- benzyl)benzenesulfonamide 788++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methyl-3-(trifluoromethyl)benzenesulfonamide 789 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2- phenylcyclopropanecarboxamide790 ++ S-ethyl 4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl- (ethyl)thiocarbamate 791 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N,3- dimethylbutamide 792 ++4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(1-naphthoyl)-2-piperidinyl]ethoxy}benzyl)- benzenesulfonamide 793 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-2-ethyl- N-methylhexanamide 794 ++4-chloro-N-[1-(2-{3-[[(4-chlorophenyl)-sulfonyl](methyl)amino]propoxy}phenyl)-ethyl]-N-(2,5-difluorophenyl)benzene- sulfonamide 795 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl sec- butylcarbamate 796 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-2,2,3,3,4,4,4-heptafluoro-N-methylbutanamide 797 ++4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(2,3,4-trifluorobenzoyl)-2-piperidinyl]ethoxy}-benzyl)benzenesulfonamide 798 ++ methyl [[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)benzyl]- (methyl)amino]acetate 799++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 2-phenylpropyl- carbamate 800 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N- methylbenzamide 801 ++4-chloro-N-(2,5-difluorophenyl)-N-[1-(2-{3-[[(ethylamino)carbonyl](methyl)amino]-ethoxy}phenyl)ethyl]benzenesulfonamide 802 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3,5- dimethoxy-N-methylbenzamide803 ++ 4-chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-methoxyphenyl)sulfinyl]propoxy}benzyl)- benzenesulfonamide 804 ++N-(3-bromophenyl)-4-chloro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 805 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-4- nitrobenzamide 806 ++3-bromo-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-propyl}-N-methylbenzenesulfonamide 807 ++4-chloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-propyl}-N-methyl-3-nitrobenzenesulfonamide 808 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2- naphthamide 809 ++N-{2-[3-(3-hydroxy-1-pyrrolidinyl)propoxy]-benzyl}-N-phenylbenzenesulfonamide hydrochloride 810 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N- methyl-2-naphthamide 811 ++4-chloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}benzamide 812 ++4-chloro-N-(2-{3-(2R, 6S)-2,6-dimethyl-piperidinyl]propoxy}benzyl)-N-phenylbenzene- sulfonamide hydrochloride813 ++ N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-2,4,5-trifluoro-N-methylbenzamide 814 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-3- methoxy-N-methylbenzamide 815++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3,5- difluorobenzamide 816 ++4-chloro-N-(3,5-dichlorophenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 817 ++4-butoxy-N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}- N-methylbenzamide 818 ++4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(phenylsulfonyl)propoxy]benzyl}benzene- sulfonamide 819 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-4- methoxybenzamide 820 ++3-bromo-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-N-methylbenzamide821 ++ N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N- methyl-1-naphthamide 822 ++3,4-dichloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-propyl}-N-methylbenzenesulfonamide 823 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyl(1S)-1-phenyl- ethylcarbamate 824 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-4- iodobenzamide 825 ++2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzylbenzylcarbamate 826 ++ phenyl 3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl(methyl)- carbamate 827 ++4-chloro-N-(cyclobutylmethyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 828 ++N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,3,4,5,6-pentafluoro-N-methylbenzamide 829 ++3-bromo-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}benzamide 830 ++S-ethyl 4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl(ethyl)- thiocarbamate 831 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N,2- diethylhexanamide 832 ++4-chloro-N-(2,5-difluorophenyl)-N-[2-(2-{1-[(2Z)-3-phenyl-2-propenoyl]-2-piperidinyl}-ethoxy)benzyl]benzenesulfonamide 833 ++4-chloro-N-(2-{3-[4-hydroxy-4-(trifluoro-methyl)-1-piperidinyl]propoxy}benzyl)-N- phenylbenzenesulfonamidehydrochloride 834 ++ N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-2,4- dimethoxy-N-methylbenzamide835 ++ 4-chloro-N-cyclopentyl-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 836 ++N-{(1R)-1-[2-(3-aminopropoxy)phenyl}ethyl}-3-chloro-N-(2,5-difluorophenyl)benzene- sulfonamide 837 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-2- ethyl N-methylhexanamide 838++ 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl benzyl[2- (dimethylamino)ethyl]carbamate839 ++ 2,4-dichloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-N-methylbenzamide840 ++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methyl[1,1′-biphenyl]-4-carboxamide 841 ++(2Z)-N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-Nmethyl-3-phenyl-2-propenamide 842 ++ 4-chloro-N-(4-hexynyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 843 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- methylacrylamide 844 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-2- cyclohexyl-N-methylacetamide 845++ N-(2-{2-[1-([1,1′-biphenyl]-4-ylcarbonyl)-2-piperidinyl]ethoxy}benzyl)-4-chloro-N-(2,5-difluorophenyl)benzenesulfonamide 846 ++N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- methyl-1-adamantanecarboxamide847 ++ 3,4-dichloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-N-methylbenzamide848 ++ 4-chloro-N-(cyclopentylmethyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 849 ++4-chloro-N-(2-{3-[[(diethylamino)carbonyl]-(methyl)amino]propoxy}benzyl)-N-(2,5- difluorophenyl)benzenesulfonamide850 ++ 4-chloro-N-{2-[2-(cyclohexylsulfanyl)ethoxy]-benzyl}-N-(2,5-difluorophenyl)benzene- sulfonamide 851 ++N-{2-[3-(1-azepanyl)propoxy]benzyl}-4- chloro-N-phenylbenzenesulfonamidehydro- chloride 852 ++ 4-chloro-N-cyclohexyl-N-{2-[3-(1-piperidinyl)-propoxy]benzyl}benzenesulfonamide hydrochloride 853 ++2,2,2-trichloro-N-{3-[2-({[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]- propyl}-N-methylacetamide854 ++ N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methyltetradecanamide 855 ++N-[(1R)-1-(2-bromophenyl)ethyl]-4-chloro-N-(2,5-difluorophenyl)benzenesulfonamide 856 ++ S-ethyl2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl- (methyl)thiocarbamate 857 ++N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-3- cyclopentyl-N-ethylpropanamide858 ++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-2-naphthamide 859 ++4-chloro-N-{2-[3-(4-morpholinyl)propoxy]-benzyl}-N-phenylbenzenesulfonamide hydro- chloride 860 ++4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(3-methylbenzoyl)-2-piperidinyl]ethoxy}benzyl)- benzenesulfonamide 861 ++4-chloro-N-(2,5-difluorophenyl)-N-((1S)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 862 ++ N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-3- fluoro-N-methylbenzamide 863++ N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-2,3,4,5 tetrafluorobenzamide 864++ N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-2,3,4-trifluoro-N-methylbenzamide 865 ++4-chloro-N-{2-[3-(2-ethyl-1-piperidinyl)-propoxy]benzyl}-N-phenylbenzenesulfonamide hydrochloride 866 ++N-(2-bromophenyl)-4-chloro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 867 ++4-chloro-N-[(1R)-1-methylbutyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 868 ++4-chloro-N-(2,5-difluoroanilino)-N-[(1S)-2-hydroxy-1-phenylethyl]benzenesulfonamide 869 ++4-chloro-N-{2-[3-(cyclohexylsulfanyl)-propoxy]benzyl}-N-(2,5-difluorophenyl)- benzenesulfonamide 870 ++4-chloro-N-{2-[3-(cyclohexylsulfanyl)-propoxy]benzyl}-N-(2,5-difluorophenyl)- benzenesulfonamide 871 ++4-chloro-N-(2,5-difluoroanilino)-N-(2-{3-[(4-methoxyphenyl)sulfonyl]propoxy}benzyl)- benzenesulfonamide 872 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N- methyl-4-nitrobenzamide 873 ++N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N-methyl-4-(trifluoromethoxy)benzamide 874 ++4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(2-vinylphenyl)ethyl]benzenesulfonamide 875 ++4-chloro-N-(2-methylphenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 876 ++2,2,2-trichloro-N-{3-[2-({[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl(methyl)carbamate877 ++ 4-chloro-N-{2-[3-(1,4-dioxa-8-azaspiro[4.5]-dec-8-yl)propoxy]benzyl}-N-phenylbenzene- sulfonamide 878 +4-chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(1-piperidinyl)propoxy]phenyl}propyl)benzene- sulfonamide hydrochloride879 + N-(2,5-difluorophenyl)-4-methoxy-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 880 +N-{2-[3-(4-benzyl-1-piperidinyl)propoxy]-benzyl}-4-chloro-N-phenylbenzenesulfonamide hydrochloride 881 +3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-1- propanesulfonic acid 882 +4-chloro-N-{2-[3-(1H-imidazol-1-yl)propoxy]-benzyl}-N-phenylbenzenesulfonamide hydro- chloride 883 +4-chloro-N-{2-[3-(1-hydroxy-[lambda˜5˜piperidin-1-yl)propoxy]benzyl}-N-phenyl- benzenesulfonamide 884 +4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(4-methylbenzoyl)-2-piperidinyl]ethoxy}benzyl)- benzenesulfonamide 885 +4-chloro-N-[1-(2-{2-[[(4-chlorophenyl)-sulfonyl](methyl)amino]propoxy}phenyl)-ethyl]-N-(2,5-difluorophenyl)benzene- sulfonamide 886 +N-benzyl-4-chloro-N-{2-[3-(1-piperidinyl)-propoxy]benzyl}benzenesulfonamide hydro- chloride 887 +4-chloro-N-(5-chloro-2-hydroxyphenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride888 + 4-chloro-N-(2,5-difluorophenyl)-N-[1-(2-{2-[[(diisopropylamino)carbonyl](methyl)amino]-ethoxy}phenyl)ethyl]benzenesulfonamide 889 +4-chloro-N-{2-[2-(1-methyl-2-piperidinyl)-ethoxy]benzyl}-N-phenylbenzenesulfonamide hydrochloride 890 +4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(3,4-dimethoxybenzoyl)-2-piperidinyl]ethoxy}- benzyl)benzenesulfonamide891 + N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N-methyl-3-(trifluoromethyl)benzamide 892 +N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methyl-2,5-bis(trifluoromethyl)benzamide 893 +N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N,4- dimethylbenzamide 894 +2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}ethyl)benzyldiethylcarbamate 895 + 4-chloro-N-(3-fluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 896 + 2,4-dichloro-N-{3-[2-({[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]-propyl}-5-fluoro-N-methylbenzamide 897 +4-chloro-N-cycloheptyl-N-{2-[3-(1- piperidinyl)propoxy]benzyl}benzene-sulfonamide hydrochloride 898 +N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N-methyl-4-(trifluoromethyl)benzamide 899 +N-(2-{2-[1-(4-butoxybenzoyl)-2-piperidinyl]-ethoxy}benzyl)-4-chloro-N-(2,5-difluoro- phenyl)benzenesulfonamide 900 +3-chloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}benzamide 901 +4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(4-iodobenzoyl)-2-piperidinyl]ethoxy}benzyl)- benzenesulfonamide 902 +4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(2-methoxybenzoyl)-2-piperidinyl]ethoxy}- benzyl)benzenesulfonamide903 + N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N-methyl-1,3-benzodioxole-5-carboxamide 904 +(2S)-2-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}-2-henylethylisonicotinate 905 + 4-chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-nitrophenyl)sulfonyl]propoxy}benzyl)benzene- sulfonamide 906 +4-chloro-N-(2,5-dichloro-3-pyridinyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 907 +N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N,4- dimethyl-3-nitrobenzamide908 + 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 909 + 4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(3-methoxybenzoyl)-2-piperidinyl]ethoxy}- benzyl)benzenesulfonamide910 + 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 3-fluorobenzyl- carbamate 911 +4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propoxy]-6-methoxy- benzyl}benzenesulfonamidehydrochloride 912 + N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(methylsulfanyl)propyl]phenyl}ethyl)-4-(methylsulfanyl)benzenesulfonamide 913 +N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-3,4,5-trimethoxy-N-methylbenzamide 914 +2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorobenzyl 2-(1- pyrrolidinyl)ethylcarbamate915 + 4-chloro-N-{2-[3-(3-hydroxy-1-piperidinyl)-propoxy]benzyl}-N-phenylbenzenesulfonamide hydrochloride 916 +4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propoxy]- benzyl}benzenesulfonamide917 + N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N-methyl-2-phenylcyclopropanecarboxamide 918 +N-{2-[2-(1-azetidinyl)propoxy]benzyl}-4-chloro-N-phenylbenzenesulfonamide hydro- chloride 919 +4-chloro-N-(3-methylphenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 920 +N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-4- (trifluoromethoxy)benzamide921 + N-(2-{2-[1-(1,3-benzodioxol-5-ylcarbonyl)-2-piperidinyl]ethoxy}benzyl)-4-chloro-N-(2,5-difluorophenyl)benzenesulfonamide 922 +4-chloro-N-(2-{3-[4-(hydroxymethyl)-1-piperidinyl]propoxy}benzyl)-N-phenylbenzene- sulfonamide hydrochloride923 + N-chloro-N-{2-[(1E)-3-oxo-3-(1-pyrrolidinyl)-1-propenyl]benzyl}-N-phenylbenzene- sulfonamide 924 +4-chloro-N-[2-(methylsulfanyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride925 + 4-chloro-N-[2-(methylsulfanyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride926 + 4-chloro-N-{2-[3-(3,5-dimethyl-1-piperidinyl)-propoxy]benzyl}-N-phenylbenzenesulfonamide hydrochloride 927 +N-{2-[3-(4-benzyl-1-piperidinyl)propoxy]-benzyl}-4-chloro-N-phenylbenzenesulfonamide hydrochloride 928 +N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- ethyltetradecanamide 929 +methyl [{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}- (methyl)amino](oxo)acetate930 + N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N,2,4- trimethylpentamide 931 +N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N-methyl-3,5-bis(trifluoromethyl)benzamide 932 +3,4-dichloro-N-{3-[2-({[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]- propyl}-N-methylbenzamide933 + 4-chloro-N-(2-{2-[1-(2,3-difluorobenzyl)-2-piperidinyl]ethoxy}benzyl)-N-(2,5-difluoro- phenyl)benzenesulfonamide934 + N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N-methyl-3,5-bis(trifluoromethyl)benzamide 935 +4-[2-((1R)-1-{4-chloro-2-[[(4-chlorophenyl)-sulfonyl](methyl)amino]phenoxy}ethyl)-5- fluorophenyl]butanoic acid936 + N-(2,5-difluorophenyl)-4-(ethylsulfanyl)-N-((1R)-1-{2-[3-(ethylsulfanyl)propyl]-4-fluoro-phenyl}ethyl)benzenesulfonamide 937 + 4-chloro-N-phenyl-N-{2-[3-(4-thio-morpholinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 938 +4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(3,4,5-trimethoxybenzoyl)-2-piperidinyl]-ethoxy}benzyl)benzenesulfonamide 939 +4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[2-(1-piperidinylmethyl)phenyl]ethyl}benzene- sulfonamide hydrochloride940 + 3-[2-(2-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}-1-methylethyl)-5-fluoro- phenyl]butanoic acid 941 +4-chloro-N-(2-{[(2S)-7-methyl-7-azabicyclo-[2.2.1]hept-2-yl]methoxy}benzyl)-N-phenyl- benzenesulfonamidehydrochloride 942 + N-(2-{2-[1-(2-bromobenzoyl)-2-piperidinyl]-ethoxy}benzyl)-4-chloro-N-(2,5-difluoro- phenyl)benzenesulfonamide 943 +N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-3- cyclopentyl-N-ethylpropanamide944 + 4-chloro-N-phenyl-N-{2-[3-(1-piperazinyl)-propoxy]benzyl}benzenesulfonamide dihydro- chloride 945 +4-chloro-N-{2-[3-(1-piperidinyl)propoxy]-benzyl}-N-(3-pyridinylmethyl)benzene- sulfonamide hydrochloride 946 +4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[1-(4-fluorobenzoyl)-2-piperidinyl]ethoxy}benzyl)- benzenesulfonamide 947 +4-chloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-2-nitrobenzamide948 + 2-chloro-5-{2-[3-(1-piperidinyl)propoxy]-benzyl}-6H-dibenzo]c,e][1,2]thiazine 5,5- dioxide hydrochloride 949 +N-{2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- ethylacrylamide 950 +3,5-dichloro-N-{3-[2-(1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]- propyl}-N-methylbenzamide951 + 4-chloro-N-(4-methylpentyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 952 +4-chloro-N-[3-(methylsulfanyl)phenyl]N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride953 + 4-chloro-N-[3-(methylsulfanyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride954 + N-[(2S)-bicyclo[2.2.1]hept-2-yl]-4-chloro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride955 + 4-chloro-N-(2-methyl-2-propenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochoride 956 +4-chloro-N-phenyl-N-(2-{3-[3-(1-piperidinyl)-propoxy]phenyl}ethyl)benzeneslfonamide hydrochloride 957 +4-chloro-N-(2,5-difluorophenyl)-N-{5-methyl-2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride958 + N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-N- methyl-3,5-dinitrobenzamide959 + N-{4-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]butyl}-N- ethylcyclopropanecarboxamide960 + N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-3,4- dimethoxy-N-methylbenzamide961 + 2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)benzyl 3,4-difluoro- benzylcarbamate 962 +4-chloro-N-{2-[2-(1-methyl-2-pyrrolidinyl)-ethoxy]benzyl}-N-phenylbenzenesulfonamide hydrochloride 963 +4-chloro-N-phenyl-N-{2-[2-(2-pyrrolidinyl)-ethoxy]benzyl}benzenesulfonamide hydro- chloride 964 +4-chloro-N-{5-chloro-2-[3-(1-piperidinyl)-propoxy]benzyl}-N-phenylbenzenesulfonamide hydrochloride 965 +4-chloro-N-{2-[3-(4-hydroxy-4-methyl-1-piperidinyl)propoxy]benzyl}-N-phenylbenzene- sulfonamide hydrochloride966 + N-{3-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}-N- methyl-1-naphthamide 967 +4-chloro-N-{2-[3-(1-piperidinyl)propoxy]-benzyl}-N-(4-pyridinylmethyl)benzene- sulfonamide hydrochloride 968 +4-chloro-N-{2-[3-(4-oxo-1-piperidinyl)-propoxy]benzyl}-N-phenylbenzenesulfonamide hydrochloride 969 +N-{(2S)-bicyclo[2.2.1]hept-2-yl]-4-chloro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride970 + 4-chloro-N-{3-[2-({[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]- propyl}-N-methylbenzamide971 + ethyl (2E)-3-[2-({[(4-chlorophenyl)sulfonyl]-anilino}methyl)phenyl]-2-propenoate 972 +4-chloro-N-phenyl-N-(2-{2-[3-(1-piperidinyl)-propoxy]phenyl}ethyl)benzenesulfonamide hydrochloride 973 +4-chloro-N-phenyl-N-{2-[4-(1-piperidinyl)-1-butynyl]benzyl}benzenesulfonamide 974 +4-chloro-N-(2,3,4,5,6-pentafluorobenzyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride975 + 4-chloro-N-(5-chloro-2-hydroxybenzyl)-N- phenylbenzenesulfonamide976 + 4-chloro-N-phenyl-N-(2-{[5-(1-piperidinyl)-pentyl]oxy}benzyl)benzenesulfonamide hydrochloride 977 +4-chloro-N-phenyl-N-{2-[4-(1-piperidinyl)-butoxy]benzyl}benzenesulfonamide hydro- chloride 978 +4-chloro-N-phenyl-N-{2-[5-(1-piperidinyl)-pentyl]benzyl}benzenesulfonamide hydro- chloride 979 +4-chloro-N-{2-[3-(cyclopropylamino)propoxy]-benzyl}-N-phenylbenzenesulfonamide hydro- chloride 980 +4-chloro-N-[(1R)-1-methylbutyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 981 +4-chloro-N-phenyl-N-{2-[4-(1-piperdinyl)-butyl]benzyl}benzenesulfonamide hydro- chloride 982 +4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(phenylsulfanyl)propoxy]benzyl}benzene- sulfonamide 983 + S-methyl2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl- (methyl)thiocarbamate 984 +4-chloro-N-(cyclopropylmethyl-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 985 +N-allyl-4-chloro-N-{2-[3-(1-piperidinyl)-propoxy]benzyl}benzenesulfonamide hydro- chloride 986 +4-chloro-N-{2-[3-(1-piperidinyl)propoxy]-benzyl}-N-tetrahydro-2H-pyran-4-ylbenzene- sulfonamide hydrochloride987 + methyl (2S)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}(phenyl)ethanoate 988 +N-(4-bromophenyl)-4-chloro-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 989 +N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-3,4,5-trimethoxy-N-methylbenzamide 990 +4-chloro-N-{5-chloro-2-[4-(1-piperidinyl)-1-butynyl]benzyl}-N-phenylbenzenesulfonamide hydrochloride 991 +4-chloro-N-(2-ethynylbenzyl)-N-phenyl- benzenesulfonamide 992 +N-(2,5-dichlorophenyl)(phenyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}methane- sulfonamide hydrochloride 993 +3-(2-{[(phenylsulfonyl)anilino]methyl}- phenyl)propanoic acid 994 +(E)-N-(2,5-dichlorophenyl)-2-phenyl-N-{2-[3-(1-piperidinyl)propoxy]benzyl}ethane- sulfonamide hydrochloride 995 +ethyl 3-(2-{[(phenylsulfonyl)anilino]methyl}- phenyl)propanoate 996 +4-chloro-N-{2-[3-(cyclohexylamino)propoxy]-benzyl}-N-phenylbenzenesulfonamide hydro- chloride 997 +4-chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-nitrophenyl)sulfanyl]propoxy}benzyl)benzene- sulfonamide 998 +4-chloro-N-(4-nitrobenzyl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 999 +4-chloro-N-{2-[3-(3,4-dihydro-2(1H)-isoquinolinyl)propoxy]benzyl}-N-phenyl- benzenesulfonamide 1000 +N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-3,5- difluoro-N-methylbenzamide1001 + N-[2-(allyloxy)benzyl]-4-chloro-N-phenyl- benzenesulfonamide1002 + 3,5-dichloro-N-{3-[2-({[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]- propyl}-N-methylbenzamide1003 + 4-chloro-N-cyclopropyl-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 1004 +2-({[(4-chlorophenyl)sulfonyl]anilino}- methyl)phenyltrifluoromethanesulfonate 1005 + N-phenyl-N-{2-[4-(1-piperidinyl)butyl]-benzyl}benzenesulfonamide 1006 +(2S)-2-({[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}-2-phenylethylnicotinate 1007 + 3-((4R)-4-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}-7-fluoro-1,2,3,4-tetrahydro-1- naphthalenyl)propanoicacid 1008 + 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{4-fluoro-2-[3-(1,4,5,6-tetrahydro-2-pyrimidinyl)-propyl]phenyl}ethyl)benzenesulfonamide hydrochloride 1009 +[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]methane- sulfonic acid 1010 +N-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-4- ethoxy-N-methylbenzamide1011 + 4-chloro-N-{5-chloro-2-[3-(4-hydroxy-1-piperidinyl)propoxy]benzyl}-N-phenylbenzene- sulfonamide hydrochloride1012 + 4-chloro-N-(2,3-dihydro-1H-inden-1-yl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride1013 + (2R)-2-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}propanoicacid 1014 + S-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl} ethanethioate 1015 +4-chloro-N-[2-(2-hydroxyphenyl)ethyl]-N- phenylbenzenesulfonamide 1016 +4-chloro-N-[2-(4-hydroxybutyl)benzyl]-N- phenylbenzenesulfonamide 1017 +4-chloro-N-[2-(4-hydroxybutyl)benzyl]-N- phenylbenzenesulfonamide 1018 +4-chloro-N-phenyl-N-[2-(3-sulfanylpropoxy)- benzyl]benzenesulfonamide1019 + 4-chloro-N-[4-(methylsulfanyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride1020 + 4-chloro-N-(2,3-dihydro-1H-inden-2-yl)-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride1021 + tert-butyl 2-{2-[3-(1-piperidinyl)propoxy]-phenyl}-1H-indole-1-carboxylate trifluoro- acetate 1022 +N-{5-[(2,5-dichloro{2-[3-(1-piperidinyl)-propoxy]benzyl}anilino)sulfonyl]-4-methyl- 1,3-thiazol-2-yl}acetamidehydrochloride 1023 + N-{5-[(2,5-dichloro{2-[3-(1-piperidinyl)-propoxy]benzyl}anilino)sulfonyl]-4-methyl- 1,3-thiazol-2-yl}acetamidehydrochloride 1024 + 2-{2-[3-(1-piperidinyl)propoxy]benzyl}-2H-naphtho[1,8-cd]isothiazol 1,1-dioxide hydro- chloride 1025 +4-chloro-N-(2,5-difluorophenyl)-N-(2-{2-[3-(1-piperidinyl)propoxy]-1-naphthyl}methyl)- benzenesulfonamidehydrochloride 1026 + 4-chloro-N-{2-[(5-chloropentyl)oxy]benzyl}-N-phenylbenzenesulfonamide 1027 +4-chloro-N-[2-(methylsulfonyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride1028 + tert-butyl 4-{3-[2-({[(4-chlorophenyl)sulfonyl]-anilino}methyl)phenoxy]propyl}-1-piperazine- carboxylate hydrochloride1029 + 4-chloro-N-(2,5-difluorophenyl)-N-(2-{3-[(4-methoxyphenyl)sulfanyl]propoxy}benzyl)- benzenesulfonamide 1030 +4-chloro-N-phenyl-N-[2-(4-pyrdinylmethoxy)- benzyl]benzenesulfonamidehydrochloride 1031 + N-phenyl-N-{2-[3-(1-piperidinyl)propyl]-benzyl}benzenesulfonamide 1032 +2-{1-[(4-flurophenyl}sulfonyl]-1H-indol-2-yl}- phenyl3-(1-piperidinyl)propyl ether trifluoro- acetate 1033 +4-chloro-N-(2,5-difluorophenyl)-N-[2-(2-{1-[4-(trifluoromethoxy)benzoyl]-2-piperidinyl}-ethoxy)benzyl]benzenesulfonamide 1034 +(2E)-3-[2-({[(4-chlorophenyl)sulfonyl]anilino}-methyl)phenyl]-N-methoxy-N-methyl-2- propenamide 1035 +(2E)-3-[2-({[(4-chlorophenyl)sulfonyl]anilino}-methyl)phenyl]-2-propenoic acid 1036 +4-chloro-N-[3-(methylsulfonyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride1037 + 1-{3-[2-({[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}methyl)phenoxy]propyl}-1- methylpiperidinium iodide1038 + 1-{3-[2-((2,5-dichloro[(4-chlorophenyl)-sulfonyl]anilino}methyl)phenoxy]propyl}-1- methylpiperidinium iodide1039 + N-[2-(3-bromopropoxy)benzyl]-4-chloro-N- phenylbenzenesulfonamide1040 + 4-chloro-N-[2-(4-hydroxy-1-butynyl)benzyl}-N-phenylbenzenesulfonamide 1041 +N-{2-[3-oxo-3-(1-piperidinyl)propyl]benzyl}- N-phenylbenzenesulfonamide1042 + N-hydroxy-3-(2-{[(phenylsulfonyl)anilino]-methyl}phenyl)propanamide 1043 +3-chloro-1-[(4-chlorophenyl)sulfonyl]-2-{2-[3-(1-piperidinyl)propoxy]phenyl}-1H-indole trifluoroacetate 1044 +4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1- piperidinyl)propyl]benzyl}-N-phenylbenzenesulfonamide 1045 +N-{(1R)-1-[2-(3-bromopropoxy)phenyl]ethyl}-4-chloro-N-(2,5-difluorophenyl)benzene- sulfonamide 1046 +4-chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 1047 + 4-chloro-N-(2,5-difluorophenyl)-N-(1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)- benzenesulfonamide 1048 +4-chloro-N-(2,5-difluorophenyl)-N-((1S)-1-{2-[3-(1H-imidazol-1-yl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 1049 + (2R, 3R)-2,4-bis[(4-methylbenzoyl)oxy]- butanedioicacid compound with 4-chloro-N- (2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1- 1050 + 4-chloro-N-{2-[2-(cyclohexylsulfinyl)ethoxy]-benzy}-N-(2,5-difluorophenyl)benzene- sulfonamide 1051 +4-chloro-N-(2,5-difluorophenyl)-N-{2-[3-(1H-imidazol-1-yl)-1-propynyl]benzyl}benzene- sulfonamide hydrochloride1052 + 4-chloro-N-(2,5-difluorophenyl)-N-[1-(2-hydroxyphenyl)ethyl]benzenesulfonamide 1053 +4-benzoyl-N-((1S)-1-{{(3-[2-({[(4-chloro-phenyl)sulfonyl]-2,5-difluoroanilino}methyl)-phenoxy]propyl}(methyl)amino]carbonyl}-5- {[5-(2-oxohexahydro- 1054 +4-chloro-N-(2,5-difluorophenyl)-N-(2-hydroxy- benzyl)benzenesulfonamide1055 + 4-chloro-N-(2,5-difluorophenyl)-N-{(1R)-1-[2-(2-hydroxyethyl)phenyl]ethyl}benzene- sulfonamide 1056 +4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)- benzenesulfonamidehydrochloride 1057 + (2R)-2-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}propyl isonicotinate 1058 +(2R)-2-{[(4-chlorophenyl)sulfonyl]-2,5- difluoroanilino}propylnicotinate 1059 + N-{3-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]propyl}- N,2,2-trimethylpropanamide1060 + ethyl (2R)-2-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}propanoate 1061 +4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1-piperidinyl)propoxy]phenyl}ethyl)- benzenesulfonamidehydrochloride 1062 + 4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-((1R)-1-{2-[3-(1-piperidinyl)-propoxy]phenyl}ethyl)benzenesulfonamide hydrochloride 1063 +4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-[4-fluoro-2-(3-hydroxypropyl)phenyl]ethyl}- benzenesulfonamide 1064 +2-[2-(1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]-N-methyl- acetamide 1065 + methyl3-[2-((1R)-1-{[(4-chlorophenyl)-sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluoro- phenyl]propanoate 1066 +4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[3-(1H-1,2,4-triazol-1-yl)propyl]phenyl}- ethyl)benzenesulfonamide1067 + 4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]butanoic acid 1068 +4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]butanoic acid 1069 +4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]butanoic acid 1070 +5-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]butanoic acid 1071 +4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(2-{4-(1,1-dioxido-4-thiomorpholinyl)sulfonyl]-butyl}-4-fluorophenyl)ethyl]benzene- sulfonamide 1072 +4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]butanoic acid 1073 +4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]butanoic acid 1074 +4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(4-[(methylsulfonyl)amino]butyl}phenyl)ethyl]- benzenesulfonamide 1075 +4-chloro-N-(2,5-difluorophenyl)-N-[(1R)-1-(4-[(ethylsulfonyl)amino]butyl}-4-fluorophenyl)- ethyl]benzenesulfonamide1076 + 4-[2-((1S)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]butanoic acid 1077 +[({4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]- butanoyl}amino)oxy]aceticacid 1078 + 4-chloro-N-(2,5-difluorophenyl)-N-((1R)-1-{2-[4-(2,2-dimethylhydrazino)-4-oxobutyl]-4-fluorophenyl}ethyl)benzenesulfonamide 1079 +4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]-N- (cyanomethoxy)butanamide1080 + 4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]butanoic acid 1081 −4-chloro-N-(2-hydroxybenzyl)-N-phenyl- benzenesulfonamide 1082 −N-{2-[3-(dimethylamino)propoxy]benzyl}-N- phenylmethanesulfonamide 1083− N-{2-[3-(dimethylamino)propoxy]benzyl}-4-nitro-N-phenylbenzenesulfonamide 1084 −N-{2-[3-(dimethylamino)propoxy]benzyl}-2-nitro-N-phenylbenzenesulfonamide 1085 −5-(dimethylamino)-N-{2-[3-(dimethylamino)-propoxy]benzyl}-N-phenyl-1-naphthalene- sulfonamide 1086 −4-chloro-N-[2-(3-hydroxy-3-methyl-1-butynyl)-benzyl]-N-phenylbenzenesulfonamide 1087 −4-chloro-N-phenyl-N-{2-[(trimethylsilyl)-ethynyl]benzyl}benzenesulfonamide 1088 −N-[2-(3-hydroxypropyl)benzyl]-N-phenyl- benzenesulfonamide 1089 −4-chloro-N-[5-chloro-2-(4-hydroxy-1-butynyl)-benzyl]-N-phenylbenzenesulfonamide 1090 −4-chloro-2-({[(4-chlorophenyl)sulfonyl]- anilino}methyl)phenyltrifluoromethane- sulfonate 1091 −4-chloro-N-phenyl-N-[2-(3-pyridinylmethoxy)- benzyl]benzenesulfonamidehydrochloride 1092 − 4-chloro-N-phenyl-N-[2-(2-pyridinylmethoxy)-benzyl]benzenesulfonamide hydrochloride 1093 −(2E)-1-N-(benzyloxy)-3-[2-({[(4-chloro-phenyl)sulfonyl]anilino}methyl)phenyl]-2- propenamide hydrochloride 1094− 4-chloro-N-[4-(methylsulfonyl)phenyl]-N-{2-[3-(1-piperidinyl)propoxy]benzyl}benzene- sulfonamide hydrochloride 1095− N-(2,5-difluorophenyl)-4-(phenylsulfanyl)-N-{2-[3-(phenylsulfanyl)propoxy]benzyl}- benzenesulfonamide 1096 − ethyl4-[2-({[(2-ntrophenyl)sulfonyl]anilino}- methyl)phenyl]butanoate 1097 −4-[2-({[(2-nitrophenyl)sulfonyl]anilino}- methyl)phenyl]butanoic acid1098 − N-{2-[2-(1-{[4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)phenoxy]ethyl}-N- methyloctadecanamide 1099 +++++4-chloro-N-(2,5-dichlorophenyl)-N-[4-nitro-1(R)-methylbutyl]benzenesulfonamide 1100 +++++4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(methylsulfonyl)amino]-1(R)-methylbutyl]- benzenesulfonamide 1101 +++++4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(methylsulfonyl)methylamino]-1(R)-methyl- butyl]benzenesulfonamide 1102+++++ 4-chloro-N-(2,5-dichlorophenyl)-N-[3-[2-[(methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylpropyl]benzenesulfonamide 1103 +++++4-chloro-N-(2,5-dichlorophenyl)-N-[4-(2-carboxy-3-thiazolidinyl)-1(R)-methylbutyl]- benzenesulfonamide 1104+++++ 4-chloro-N-(2,5-dichlorophenyl)-N-[5-(1,1-dioxido-4-thiomorpholinyl)-1(R)-methyl- propyl]benzenesulfonamide 1105+++++ 4-chloro-N-(2,5-dichlorophenyl)-N-[4-(2-methoxycarbonyl-3-thiazolidinyl)-1(R)-methyl- butyl]benzenesulfonamide1106 +++++ 4-chloro-N-(2,5-dichlorophenyl)-N-[4-(2-carboxy-3-thiazolidinyl)-1(R)-methylpentyl]- benzenesulfonamide 1107+++++ 4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-nitro-1(R)-methylbutyl]benzenesulfonamide 1108 +++++4-chloro-N-(2,5-dichlorophenyl)-N-[4-[(3-methylsulfonyl)-1-piperidinyl]-1(R)-methyl- butyl]benzenesulfonamide1109 +++++ 4-chloro-N-(2,5-dichlorophenyl)-N-[4-[(3-methylsulfonyl)-1-piperidinyl]-1(R)-methyl- butyl]benzenesulfonamide1110 +++++ 4-chloro-N-(2,5-dichlorophenyl)-N-[4-nitro-1(R)-methylbutyl]benzenesulfonamide 1111 ++++4-chloro-N-(2,5-dichlorophenyl)-N-[3-(2-carboxy-3-thiazolidinyl)-1(R)-methylpropyl]- benzenesulfonamide 1112++++ 4-chloro-N-(2,5-dichlorophenyl)-N-[5-[(3-methylsulfonyl)-1-pyrrolidinyl]-1(R)-methyl- pentyl]benzenesulfonamide1113 ++++ 4-chloro-N-(2,5-dichlorophenyl)-N-[4-(acetyl-amino)-1(R)-methylbutyl]benzenesulfonamide 1114 ++++4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-(4-morpholinyl)-1-methylbutyl]benzene- sulfonamide 1115 ++++4-chloro-N-(2,5-dichlorophenyl)-N-[5-[(3-methylsulfonyl)-1-piperidinyl]-1(R)-methyl- pentyl]benzenesulfonamide1116 ++++ 4-chloro-N-(2,5-dichlorophenyl)-N-[5-[[2-[(methylsulfonyl)-1-piperidinyl]-1(R)-methyl- pentyl]benzenesulfonamide1117 ++++ 4-chloro-N-(2,5-dichlorophenyl)-N-[5-(2-methoxycarbonyl-3-thiazolidinyl)-1(R)-methyl- pentyl]benzenesulfonamide1118 ++++ 4-chloro-N-(2,5-dichlorophenyl)-N-[3-[(3-methylsulfonyl)-1-piperidinyl]-1(R)-methyl- propyl]benzenesulfonamide1119 ++++ 4-chloro-N-(2,5-dichlorophenyl)-N-[3-(2-methoxycarbonyl-3-thiazolidinyl)-1(R)-methyl- propyl]benzenesulfonamide1120 ++++ 4-chloro-N-(2,5-difluorophenyl)-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylbutyl]benzenesulfonamide 1121 +++4-chloro-N-(2,5-dichlorophenyl)-N-[4-[2-[(methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylbutyl]benzenesulfonamide 1122 +++4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylbutyl]benzenesulfonamide 1123 +++4-chloro-N-(2,5-dichlorophenyl)-N-[5-[(4-methylsulfonyl)-1-piperidinyl]-1(R)-methyl- pentyl]benzenesulfonamide1124 +++ 4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[[(S)hydroxy]phenylmethyl]carbonyl]-amino]-1(R)-methylbutyl]benzenesulfonamide 1125 +++4-chloro-N-(2,5-difluorophenyl)-N-[3-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylpropyl]benzenesulfonamide 1126 +++4-chloro-N-(2,5-dichlorophenyl)-N-[4-[(4-methylsulfonyl)-1-piperidinyl]-1(R)-methyl- butyl]benzenesulfonamide1127 +++ 4-chloro-N-(5-chloro-2-fluorophenyl)-N-[3-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylpropyl]benzenesulfonamide 1128 +++4-chloro-N-(2,5-dichlorophenyl)-N-[4-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylbutyl]benzenesulfonamide 1129 +++4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[[(R)hydroxy]phenylmethyl]carbonyl]-amino]-1(R)-methylbutyl]benzenesulfonamide 1130 +++4-chloro-N-(5-chloro-2-fluorophenyl)-N-[3-[2-[4-chloro-N-(5-chloro-2-fluorophenyl)-N-[(3-amino)-1(R)-methylpropyl]benzene-sulfonamide]-3,4-dioxo-1-cyclobutenyl)amine- 1(R)- 1131 +++4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[(methoxy)carbonyl]amino]-1-methylbutyl]- benzenesulfonamide 1132 +++4-chloro-N-(2,5-dichlorophenyl)-N-[3-[(3-methylsulfonyl)-1-piperidinyl]-1(R)-methyl-propyl]benzenesulfonamide 1133 +++4-chloro-N-(2,5-dichlorophenyl)-N-[3-(2-methoxycarbonyl-3-thiazolidinyl)-1(R)-methyl- propyl]benzenesulfonamide1134 ++ 4-chloro-N-(2,5-dichlorophenyl)-N-[4-[(3-methylthio)-1-pyrrolidinyl]-1(R)-methylbutyl]- benzenesulfonamide 1135++ 4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[N-(cyclopropylmethyl)-N-[3-(1H-imidazol-1-yl)-propyl]amino]-1(R)-methylbutyl]benzene- sulfonamide 1136 ++4-chloro-N-(2,5-dichlorophenyl)-N-[4-[3-[(methylsulfonyl)-1-piperidinyl]-1(R)-methyl- butyl]benzenesulfonamide1137 ++ 4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[(1,1-dimethylethyl)carbonyl]amino]-1-methylbutyl]- benzenesulfonamide 1138 ++4-chloro-N-(2,5-dichlorophenyl)-N-[4-(azido)-1-methylbutyl]benzenesulfonamide 1139 ++4-chloro-N-(2,5-difluorophenyl)-N-[3-[2-[4-chloro-N-(2,5-difluorophenyl)-N-[(3-amino)-1(R)-methylpropyl]benzenesulfonamide]-3,4-dioxo-1-cyclobutenyl)amine-1(R)- 1140 ++4-chloro-N-(2,5-dichlorophenyl)-N-[4-[3-[(methylsulfonyl)-1-piperidinyl]-1(R)-methyl- pentyl]benzenesulfonamide1141 ++ 4-chloro-N-(2,5-difluorophenyl)-N-[3-(2-isopropoxy-3,4-dioxo-1-cyclobutenyl)amine-1(R)-methylpropyl]benzenesulfonamide 1142 ++4-chloro-N-(2,5-dichlorophenyl)-N-[3-[(3-methylthio)-1-piperidinyl]-1(R)-methyl- propyl]benzenesulfonamide 1143++ 4-chloro-N-(2,5-dichlorophenyl)-N-[3-[2-[4-chloro-N-(2,5-dichlorophenyl)-N-[(3-amino)-1(R)-methylpropyl]benzenesulfonamide]-3,4-dioxo-1-cyclobutenyl)amine-1(R)- 1144 ++4-chloro-N-(2,5-dichlorophenyl)-N-[4-[(4-methylthio)-1-pyrrolidinyl]-1(R)-methylbutyl]- benzenesulfonamide 1145++ 4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[(1,1-dimethylethoxy)carbonyl]amino]-1-methyl- butyl]benzenesulfonamide 1146++ 4-chloro-N-(2,5-dichlorophenyl)-N-[3-[(4-methylsulfonyl)-1-piperidinyl]-1(R)-methyl- propyl]benzenesulfonamide1147 ++ 4-chloro-N-(2,5-dichlorophenyl)-N-[3-[(3-methylthio)-1-pyrrolidinyl]-1(R)-methyl- propyl]benzenesulfonamide 1148++ 4-chloro-N-(2,5-dichlorophenyl)-N-[4-[3-[(methylthio)-1-pyrrolidinyl]-1(R)-methyl- butyl]benzenesulfonamide 1149++ 4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[(phenyl)carbonyl]amino]-1-methylbutyl]- benzenesulfonamide 1150 ++4-chloro-N-(2,5-dichlorophenyl)-N-[5-[[4-(methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylpentyl]benzenesulfonamide 1151 ++4-chloro-N-(2,5-dichlorophenyl)-N-[3-[(3-(methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylpropyl)benzenesulfonamide 1152 ++4-chloro-N-(2,5-dichlorophenyl)-N-(4-amino)-1-methylbutyl]benzenesulfonamide 1153 ++4-chloro-N-(2,5-dichlorophenyl)-N-[4-[(3-methylthio)-1-piperidinyl]-1(R)-methylbutyl]- benzenesulfonamide 1154 ++4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[(phenoxy)carbonyl]amino]-1-methylbutyl]- benzenesulfonamide 1155 ++4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[(benzoxy)carbonyl]amino]-1-methylbutyl]- benzenesulfonamide 1156 ++4-chloro-N-(2,5-dichlorophenyl)-N-[3-[(4-methylthio)-1-piperidinyl]-1(R)-methylpropyl]- benzenesulfonamide 1157++ 4-chloro-N-(2,5-dichlorophenyl)-N-[4-[[4-(methylsulfonyl)methyl]-1-piperidinyl]-1(R)-methylbutyl)benzenesulfonamide 1158 +4-chloro-N-(2,5-dichlorophenyl)-N-[4-[N-(2,5-dichlorophenyl)-N-[(4-chlorophenyl)sulfonyl]-amino]-1(R)-methylbutyl]benzenesulfonamide 1159 +4-chloro-N-(2,5-dichlorophenyl)-N-[3-[[3-(methylthio)-1-piperidinyl]-1(R)-methyl- propyl]benzenesulfonamide 1160+++++ 4-chloro-N-(5-chloro-2-fluorophenyl)-N-[1(R)-methyl-(4-ethylsulfinyl)butyl]benzene- sulfonamide 1161 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(1-methylethyl)sulfonyl]butyl]- benzenesulfonamide 1162 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-methylsulfonyl]butyl]benzene- sulfonamide 1163 +++++4-chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)-methyl-(4-ethylsulfonyl)butyl]benzene- sulfonamide 1164 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-ethylsulfonyl]butyl]benzene- sulfonamide 1165 +++++4-chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)-methyl-(4-methylsulfonyl)butyl]benzene- sulfonamide 1166 +++++4-chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-ethylsulfonyl)butyl]benzene- sulfonamide 1167 +++++4-chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)-methyl-(4-methylsulfinyl)butyl]benzene- sulfonamide 1168 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(5-ethylsulfonyl)butyl]benzene- sulfonamide 1169 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(1-methylethyl)sulfinyl]butyl]- benzenesulfonamide 1170 +++++4-chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-methylsulfonyl)butyl]benzene- sulfonamide 1171 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-methylsulfinyl)butyl]benzene- sulfonamide 1172 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-ethylsulfinyl)butyl]benzene- sulfonamide 1173 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(5-ethylsulfinyl)pentyl]benzene- sulfonamide 1174 +++++4-chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-ethylsulfinyl)butyl]benzene- sulfonamide 1175 +++++4-chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-methylsulfinyl)butyl]benzene- sulfonamide 1176 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-methylthio)butyl]benzene- sulfonamide 1177 +++++4-chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-ethylthio)butyl]benzenesulfonamide 1178 +++++4-chloro-N-[5-chloro-2-fluorophenyl]-N-[1(R)-methyl-(4-methylthio)butyl]benzene- sulfonamide 1179 +++++4-chloro-N-[2,5-difluorophenyl]-N-[1(R)-methyl-(4-[(1-methylethyl)sulfinyl]butyl]- benzenesulfonamide 1180 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(3-ethylsulfonyl)propyl]benzene- sulfonamide 1181 +++++(6R)-6-[(2,5-dichlorophenyl)-[(4-chloro-phenyl)sulfonyl]-amino]-3-thioheptanoic acid 1182 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(2-methylpropyl)sulfinyl]butyl]- benzenesulfonamide 1183+++++ 4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-ethylthio)butyl]benzenesulfonamide 1184 ++++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(2-methylpropyl)sulfonyl]butyl]- benzenesulfonamide 1185 ++++methyl(6R)-6-[(2,5-dichlorophenyl)-[(4-chloro-phenyl)sulfonyl]-amino]-3-thioheptanoic 1186 ++++(5R)-5-[(2,5-dichlorophenyl)-[(4-chloro-phenyl)sulfonyl]-amino]-3-thioheptanoic acid 1187 +++methyl(6R)-6-[(2,5-dichlorophenyl)-[(4-chloro-phenyl)sulfonyl]-amino]-3-thioheptanoic acid, 3-oxide 1188 ++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4-[(2-methylpropyl)thio)sulfonyl]- butyl]benzenesulfonamide 1189++ 4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(3-ethylthio)propyl]benzenesulfonamide 1190 ++4-chloro-N-[2,5-dichlorophenyl]-N-[1(R)-methyl-(4[(1-methylethyl)thio]butyl]benzene- sulfonamide 1191 ++methyl(6R)-6-[(2,5-dichlorophenyl)-[(4-chloro-phenyl)sulfonyl]-amino]-3-thioheptanoic acid, 3,3-dioxide 1192 ++(4R)-4-[N-[5-chloro-2-fluorophenyl][(4-chlorophenyl)sulfonyl]amino]pentylsulfonic acid 1193 ++methyl(6R)-6-[(2,5-dichlorophenyl)-[(4-chloro-phenyl)sulfonyl]-amino]-3-thioheptanoic acid, 3-oxide 1194 ++(4R)-4-[N-[2,5-dichlorophenyl][(4-chloro-phenyl)sulfonyl]amino]pentylsulfonic acid 1195 +methyl(4R)-4-[N-[2,5-dichlorophenyl][(4-chlorophenyl)sulfonyl]amino]pentylsulfonate 1196 +(6R)-6-[(2,5-dichlorophenyl)-[(4-chloro-phenyl)sulfonyl]-amino]-3-thioheptanoic acid, 3-oxide 1197 +(6R)-6-[(2,5-dichlorophenyl)-[(4-chloro-phenyl)sulfonyl]-amino]-3-thioheptanoic acid, 3,3-dioxide 1198 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(1-azetidinyl)sulfonyl]-1(R)-methylbutyl]- benzenesulfonamide 1199 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]- benzenesulfonamide 1200 +++++4-chloro-N-[2,5-difluorophenyl]-N-[4-[(1-azetidinyl)sulfonyl]-1(R)-methylbutyl]- benzenesulfonamide 1201 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(dimethylamino)sulfonyl]-1(R)-methylbutyl]- benzenesulfonamide 1202+++++ 4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[(dimethylamino)sulfonyl]-1(R)-methylbutyl]- benzenesulfonamide 1203+++++ 4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]- benzenesulfonamide 1204 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(1-pyrrolidinyl)sulfonyl]-1(R)-methylbutyl]- benzenesulfonamide 1205 +++++4-chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[(1-pyrrolidinyl)sulfonyl]-1(R)-methylbutyl]- benzenesulfonamide 1206 +++++4-chloro-N-[2,5-difluorophenyl]-N-[4-[(dimethylamino)sulfonyl]-1(R)-methylbutyl]- benzenesulfonamide 1207+++++ 4-chloro-N-[2,5-difluorophenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]- benzenesulfonamide 1208 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(ethylamino)sulfonyl]-1(R)-methylbutyl]- benzenesulfonamide 1209 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(4-morpholinyl)sulfonyl]-1(R)-methylbutyl]- benzenesulfonamide 1210+++++ N-[4-(aminosulfonyl)-1(R)-methylbutyl]-4-chloro-N-(2,5-dichlorophenyl)benzene- sulfonamide 1211 +++++4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(4-thiomorpholinyl)sulfonyl]-1(R)-methyl- butyl]benzenesulfonamide 1212+++++ 4-chloro-N-[2,5-dichlorophenyl]-N-[4-[[N-(1-methylethyl)methylamino]sulfonyl]-1(R)- methylbutyl]benzenesulfonamide1213 +++++ 4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(diethylamino)sulfonyl]-1(R)-methylbutyl]- benzenesulfonamide 1214+++++ 4-chloro-N-[2,5-dichlorophenyl]-N-[4-[[(tetrahydro-1,1-dioxido-3-thienyl)amino]-sulfonyl]-1(R)-methylbutyl]benzene- sulfonamide 1215 ++++4-chloro-N-[2,5-dichlorophenyl]-N-[4-[[(N-cyclopentyl)methylamino]sulfonyl]-1(R)-methylbutyl]benzenesulfonamide 1216 +++4-chloro-N-[2,5-dichlorophenyl]-N-[4-[(2-methylpropylamino)sulfonyl]-1(R)- methylbutyl]benzenesulfonamide1217 +++++ 4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-ethylsulfonyl)- butyl]benzenesulfonamide 1218+++++ 4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-[(1,1-dimethyl-ethyl)sulfonyl]butyl]benzenesulfonamide 1219 +++++4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-[(1-methyl-ethyl)sulfinyl]butyl]benzenesulfonamide 1220 +++++4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-[(1-methyl-ethyl)sulfonyl]butyl]benzenesulfonamide 1221 +++++4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-[(1,1-dimethyl-ethyl)sulfinyl]butyl]benzenesulfonamide 1222 +++++4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-ethylsulfinyl)- butyl]benzenesulfonamide 1223+++++ 4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-[(1-methyl-ethyl)thio]butyl]benzenesulfonamide 1224 +++++4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-methylsulfinyl)- butyl]benzenesulfonamide 1225+++++ 4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-methylsulfonyl)- butyl]benzenesulfonamide 1226+++++ 4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-phenylthio)- butyl]benzenesulfonamide 1227+++++ 4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-ethylthio)- butyl]benzenesulfonamide 1228+++++ 4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-methylthio)- butyl]benzenesulfonamide 1229+++++ 4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-[(1,1-dimethyl-ethyl)thio]butyl]benzenesulfonamide 1230 ++++4-methylsulfonyl-N-[5-chloro-2-(hydroxy-methyl)phenyl]-N-1(R)-methyl-(4-methyl-sulfonyl)butyl]benzenesulfonamide 1231 ++(4R)-4-[N-[5-chloro-2-(hydroxymethyl)-phenyl][(4-chlorophenyl)sulfonyl]amino]pentyl- sulfonic acid 1232 +4-ethylthio-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[1(R)-methyl-(4-ethylthio)butyl]- benzenesulfonamide 1233+++++ 4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[4-[(methylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide 1234 +++++4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[4-[(dimethylamino)sulfonyl]-1(R)-methylbutyl]benzenesulfonamide 1235 +++++4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[4-(aminosulfonyl)-1(R)-methyl- butyl]benzenesulfonamide 1236++ 4-chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[4-[N-(cyclopropylmethyl)-N-[3-(1H-imidazol-1-yl)-propyl]aminosulfonyl]-1(R)-methylbutyl]benzenesulfonamide 1237 +++++4-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[[pyrrolidin-1-yl]carbonyl]oxy]-R-1-methyl- ethyl]benzenesulfonamide1238 +++++ 4-Chloro-N-(2,5-difluorophenyl)-N-[2-[[[pyrrolidin-1-yl]carbonyl]oxy]-R-1-methyl- ethyl]benzenesulfonamide1239 +++++ 4-Chloro-N-(2,5-difluorophenyl)-N-[2-[[N′-[3-(1H-imidazol-1-yl)propylamino]-carbonyl]oxy]-(R)-1-methylethyl]benzene- sulfonamide 1240 +++++4-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[N′-[3-(1H-imidazol-1-yl)propylamino]-carbonyl]oxy]-(R)-1-methylethyl]benzene- sulfonamide 1241 +++++4-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[[(S)-2-(hydroxymethyl)pyrrolidin-1-yl)]-carbonyl]oxy]-(R)-1-methylethyl]benzene- sulfonamide 1242 +++++4-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[N′-2-(piperidin-1-yl)ethylamino]carbonyl]-oxy]-(R)-1-methylethyl]benzenesulfonamide 1243 +++++4-Chloro-N-(2-fluoro-5-chlorophenyl)-N-[2-[[[pyrrolidin-1-yl]carbonyl]oxy]-(R)-1- methylethyl]benzenesulfonamide1244 +++++ 4-Chloro-N-(2-fluoro-5-chlorophenyl)-N-[2-[[N′-[3-(1H-imidazol-1-yl)propylamino]-carbonyl]oxy]-(R)-1-methylethyl]benzene- sulfonamide 1245 +++++4-Chloro-N-(2-fluoro-5-chlorophenyl)-N-[2-[[N′-[2-(1H-imidazol-4-yl)ethylamino]-carbonyl]oxy]-(R)-1-methylethyl]benzene- sulfonamide 1246 +++++4-Chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[2-[[N′-[3-(1H-imidazol-1-yl)-propylamino]carbonyl]oxy]-(1R)-(2R)- dimethylethyl]benzenesulfonamide1247 +++++ 4-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[[N′-[3-(1H-imidazol-1-yl)propyl]-N′-ethylamino]carbonyl]oxy]-(R)-1-methylethyl]- benzenesulfonamide 1248+++++ 4-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[N′-[3-(1H-tetrazol-1-yl)propylamino]-carbonyl]oxy]-(R)-1-methylethyl]benzene- sulfonamide 1249 +++++4-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[N′-[2-(hydroxyethyl)-N′-methylamino]-carbonyl]oxy]-(R)-1-methylethyl]benzene- sulfonamide 1250 +++++4-Chloro-N-(2,5-dichlorophenyl)-N-[2-[[[N′-[3-(1H-imidazol-1-yl)propyl]-N′-methyl-amino]carbonyl]oxy]-(R)-1-methylethyl]- benzenesulfonamide 1251 +++++4-Chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[2-[[[N′-[3-(1H-imidazol-1-yl)-propyl]-N′-cyclopropylmethylamino]carbonyl]-oxy]-(R)-1-methylethyl]benzenesulfonamide 1252 +++++4-Chloro-N-[5-chloro-2-(hydroxymethyl)-phenyl]-N-[2-[[[N′-[3-(1H-imidazol-1-yl)-propyl]-N′-(2-methylethyl)amino]carbonyl]-oxy]-(R)-1-methylethyl]benzenesulfonamide 1253 ++4-chloro-N-(2,5-dichlorophenyl)-N-[1-(S)-[2-(methylsulfonyl)ethyl]pyrrolidin-2-yl]ethyl]- benzenesulfonamide 1254 +4-chloro-N-(2,5-dichlorophenyl)-N-[1-(S)-pyrrolidin-2-yl]ethyl]benzenesulfonamide 1255 +4-chloro-N-(2,5-dichlorophenyl)-N-[1-(S)-[1-[(1,1-dimethylethoxy)carbonyl]pyrrolidin-2-yl]- ethyl]benzenesulfonamide1256 ++ (R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[N-(S)-[1-(methoxycarbonyl)-3-methyl-butyl]amino]-1-methyl-4-oxobutyl]benzene- sulfonamide 1257 +++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[4-[N-(S)-[1-(methoxycarbonyl)-2-methyl-propyl]amino]-1-methyl-4-oxobutyl]benzene- sulfonamide 1258 +++++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[6-[N-(S)-[1-(methoxycarbonyl)-3-methyl-butyl]amino]-1-methyl-6-oxohexyl]benzene- sulfonamide 1259 +++++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[6-[N-(S)-[1-(carboxy)-3-methylbutyl]-amino]-1-methyl-6-oxohexyl]benzene- sulfonamide 1260 +++++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[6-[N-(S)-[1-(methoxycarbonyl)-3-methyl-butyl]amino]-1-methyl-6-oxohexyl]benzene- sulfonamide 1261 +++++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[6-[N-(S)-[1-(methoxycarbonyl)-2-methyl-propyl]amino]-1-methyl-6-oxohexyl]benzene- sulfonamide 1262 +++++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[6-[N-(S)-[1-(carboxy)-2-methylpropyl]-amino]-1-methyl-6-oxohexyl]benzene- sulfonamide 1263 ++++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[6-[N-(S)-[1-(carboxy)-3-methylbutyl]-amino]-1-methyl-6-oxohexyl]benzene- sulfonamide 1264 ++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(S)-[1-(methoxycarbonyl)-2-methyl-propyl]amino]-1-methyl-6-oxopentyl]benzene- sulfonamide 1265 +++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[6-[N-(S)-[1-(methoxycarbonyl)-3-methyl-butyl]amino]-1-methyl-5-oxopentyl]benzene- sulfonamide 1266 +++++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(R)-[1-(methoxycarbonyl)-2-methyl-propyl]amino]-1-methyl-5-oxopentyl]benzene- sulfonamide 1267 ++++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(R)-[1-(methoxycarbonyl)-3-methyl-butyl]amino]-1-methyl-5-oxopentyl]benzene- sulfonamide 1268 ++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(S)-[1-(carboxy)-2-methylpropyl]-amino]-1-methyl-5-oxopentyl]benzene- sulfonamide 1269 ++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(S)-[1-(carboxy)-3-methylbutyl]-amino]-1-methyl-5-oxopentyl]benzene- sulfonamide 1270 ++++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(R)-[1-(carboxy)-2-methylpropyl]-amino]-1-methyl-5-oxopentyl]benzene- sulfonamide 1271 +++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[5-[N-(R)-[1-(carboxy)-3-methylbutyl]-amino]-1-methyl-5-oxopentyl]benzene- sulfonamide 1272 +++++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[1-(methyl-6-(1,1-dioxo-2-methyl-4-thio-morpholinyl)-6-oxohexyl]benzenesulfonamide 1273 +++++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[1-(methyl-6-(1,1-dioxo-3-methyl-4-thio-morpholinyl)-6-oxohexyl]benzenesulfonamide 1274 +++++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[1-(methyl-6-(1,1-dioxo-2-methyl-4-thio-morpholinyl)hexyl]benzenesulfonamide 1275 +++++(R)-4-Chloro-N-(5-chloro-2-fluorophenyl)-N-[1-(methyl-6-(1,1-dioxo-3-methyl-4-thio-morpholinyl)hexyl]benzenesulfonamide 1276 +++++(R)-4-Chloro-N-(2,5-difluorophenyl)-N-[1-[4-fluoro-2-[1-(2-methyl-4-thiomorpholinyl)-butanoyl]phenyl]ethyl]benzenesulfonamide 1277 +++++(R)-4-Chloro-N-(2,5-difluorophenyl)-N-[1-[4-fluoro-2-[1-(1,1-dioxo-2-methyl-4-thio-morpholinyl)butanoyl]phenyl]ethyl]- benzenesulfonamide 1278 +++++(R)-4-Chloro-N-(2,5-difluorophenyl)-N-[1-[4-fluoro-2-[1-(1,1-dioxo-2-methyl-4-thio-morpholinyl)butyl]phenyl]ethyl]benzene- sulfonamide

NUMBER COMPOUND ACTIVITY 1279

+++++ 1280

+++++ 1281

+++++ 1282

+++++ 1283

+++++ 1284

+++++ 1285

+++++ 1286

+++++ 1287

+++++ 1288

+++++ 1289

+++++ 1290

+ 1291

+++++ 1292

− 1293

− 1294

+++++ 1295

+++++ 1296

− 1297

+++++ 1298

+++++ 1299

++ 1300

++ 1301

+ 1302

+ 1303

++ 1304

++ 1305

+ 1306

+ 1307

++ 1308

++ 1309

+ 1310

+ 1311

+ 1312

+ 1313

++ 1314

++ 1315

+ 1316

+ 1317

+ 1318

+ 1319

+ 1320

++ 1321

++ 1322

+ 1323

+ 1324

+ 1325

+ 1326

+ 1327

+ 1328

++ 1329

+ 1330

+ 1331

+ 1332

++ 1333

+ 1334

+ 1335

+ 1336

+ 1337

+ 1338

++ 1339

++ 1340

+ 1341

++ 1342

++ 1343

+ 1344

++ 1345

++ 1346

++ 1347

++ 1348

+ 1349

++ 1350

++ 1351

+ 1352

+ 1353

+ 1354

+ 1355

+ 1356

+ 1357

++ 1358

++ 1359

+ 1360

++ 1361

+ 1362

+ 1363

+ 1364

+ 1365

+ 1366

+

Inspection of the extensive dates presented in the preceding Tablereveals that a wide variety of compounds of the generic formula providedherein display activity in an in vitro cell-based assay.

While the invention has been described in detail with reference tocertain preferred embodiments thereof, it will be understood thatmodifications and variations are within the spirit and scope of thatwhich is described and claimed.

1. A compound having the structure:

and pharmaceutically acceptable salts thereof, wherein: D is hydrogen orlower alkyl; E is substituted or unsubstituted phenyl; G is substitutedor unsubstituted phenyl; and J is substituted phenyl, comprising one ormore substituents selected from the group consisting of methyl, alkylsubstituted by one or more substituents selected from cycloalkyl,cycloalkenyl, aryl, heterocycle, cyano, cyanomethyl, nitro, amino,amide, amidine, hydroxyl, carboxyl, carbamate, ether, ester, sulfonyl,sulfonamide and mercapto, halogen, ether, —S-alkyl, or —S-aryl.
 2. Thecompound of claim 1, wherein: substituent(s) on E is(are) independentlysubstituted or unsubstituted alkyl, halogen, hydroxy, ester, —S-alkyl,NO₂ or SO₂; substituent(s) on G is(are) independently substituted orunsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, halogen, amide,amine, hydroxy, sulfonyl, sulfonamide, —(CH₂)_(n)—O—(CH₂)_(m)-amine,—(CH₂)_(n)—O—(CH₂)_(m)-heterocycle, or —(CH₂)_(n)—O—(CH₂)_(m)-amide,wherein n and m are independently 0, 1, 2, 3, 4 or 5; and substituent(s)on J is(are) independently methyl, halogen, ether, —S-alkyl, or —S-aryl.3. The compound of claim 2, wherein: substituent(s) on B and J is(are)halogen; and substituent(s) on G is(are) halogen and/or substitutedalkyl.
 4. A composition comprising a compound according to claim 1 in apharmaceutically acceptable carrier therefor.